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In terms of risk assessment especially for known and unknown substances migrating from food contact materials, quantification without corresponding reference substances currently poses a challenge. In the present study, the opportunity of a universal response quantification approach was evaluated by using a corona charged aerosol detector (CAD) for liquid chromatography combined with inverse gradient compensation. Characteristics of CAD detection in dependence of substance properties were analyzed with 46 randomly chosen reference substances. An almost equal CAD response (±20%) was achieved for non-volatile substances with a molecular weight of minimum 400 g/mol and a vapor pressure of maximum 10−8 Torr. We empirically defined an analytical parameter, Q50/35, the quotient of CAD peak areas at CAD evaporator temperatures of 50 °C and 35 °C, to predict the adequacy of the CAD universal response approach for quantification of known and unknown analyte substances. Exemplarily, we applied the CAD universal quantification approach for the determination of extractable oligomers below 1000 g/mol from a variety of food contact polycondensate plastic materials (e.g. polyesters like polyethylene terephthalate, polybutylene terephthalate, Tritan copolyester, polyamides 6, 6.6 and 6 T/6I and polyarylsulfones polyphenylsulfone and polyethersulfone). Quantitative results for in total 44 oligomers out of 11 materials were compared with established material-specific quantification methods using extracted oligomer mixtures as well as individual oligomers isolated from the mixtures. CAD-based quantification results were generally in accordance to published quantification approaches for polyamide oligomers and oligomers from polyarylsulfones. For oligomers extracted and isolated from polyester materials a slight underestimation was determined by CAD universal response approach. In terms of detection limits and accuracy, the universal CAD approach exhibits no advantages compared to established UV-methods, to date.
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... Terephthalic acid (>98%) was from Merck. Bis(2-hydroxyethyl) terephthalate (BHET, 94.7%; purity (UV 220 nm) was determined as a peak area percentage (Eckardt et al. 2018), since no information on the purity was available from the manufacturer) was purchased from TCI. PBT cyclic dimer (CT 2 B 2 , 99%) and trimer (CT 3 B 3 , 98%) were self-isolated and characterized (Eckardt et al. 2018). ...
... Terephthalic acid (>98%) was from Merck. Bis(2-hydroxyethyl) terephthalate (BHET, 94.7%; purity (UV 220 nm) was determined as a peak area percentage (Eckardt et al. 2018), since no information on the purity was available from the manufacturer) was purchased from TCI. PBT cyclic dimer (CT 2 B 2 , 99%) and trimer (CT 3 B 3 , 98%) were self-isolated and characterized (Eckardt et al. 2018). ...
... Therefore, semi-quantification using a commercially available substance is usually an option. Eckardt et al. (2018) presented a quantification approach based on charged aerosol detection (CAD). CAD has an almost uniform response to non-volatile substances, independent of their chemical structure, making their semi-quantification with an uncertainty of 20% by any other non-volatile standard substance possible. ...
Article
Oligomers are a significant group of migrating substances from food contact materials made of polyesters like polybutylene terephthalate (PBT). Twenty-three cyclic and linear oligomers with different end groups including olefin-terminated oligomers, which are associated with thermal stress of the material, were tentatively identified in PBT extracts by high-performance liquid chromatography with mass spectrometry and diode array detection. Quantification approaches based on chromophore concentration, relative response factors, and overall oligomer determination after hydrolysis to the monomer terephthalic acid were employed. An exhaustive extraction of thirteen PBT samples yielded an overall oligomer content of 1.87–6.10 mg/g material (sum of individual oligomers < 1,000 Da) with a predominant content of cyclic over linear oligomers. Migration experiments were performed according to Regulation (EU) No. 10/2011 using the official food simulants as well as cows’ milk. A total of 218 µg cyclic oligomers/L milk were detected in the third migrate relevant for risk assessment of repeated-use articles under hot-fill conditions (70 °C, 2 h). The official food simulant for milk, 50% ethanol, was found to overestimate the actual migration into milk by a factor of four. Frying conditions using sunflower oil as the food simulant (200 °C, 10 min) resulted in a migration of 7.5 mg cyclic oligomers/kg oil. The exposure to migrating oligomers is critical in some scenarios when evaluated by the threshold of toxicological concern concept; however, the toxicological evaluation poses a challenge due to the possible hydrolysis of cyclic oligomers in the human gastrointestinal tract. Our experiments display the need for a toxicological evaluation of PBT oligomers because the migration of cyclic oligomers is expected to exceed the current in silico–based thresholds under foreseeable conditions of use.
... presented a pragmatic chromophore concentration approach for aromatic polyester oligomers based on TPA and/ or IPA using a UV detector calibrated with a commercially available linear oligomer reference bis(2-hydroxyethyl) terephthalate (BHET). Eckardt et al. (2018) demonstrated with a Corona charged aerosol detector (CAD) and isolated oligomers that the chromophore concentration approach may lead to a slight overestimation for individual polyester oligomers but is generally suitable to estimate the concentration of a great variety of polyester oligomers. Paseiro-Cerrato et al. (2016b) used both HPLC-MS and diode array detection (DAD) calibrated with the polyethylene terephthalate (PET) cyclic trimer and short chained commercial linear oligomers like BHET to estimate the concentration of oligomers extracted from a can coating. ...
... Exposure thresholds given by the TTC concept were transferred to analytical thresholds for the migration of substances from the coatings considering the daily dietary intake of infants. A Corona CAD with an inverse gradient compensation (inverse gradient offset: 1514 µL for M1 and 933 µL for M2) was used as universal HPLC detector exhibiting an almost equal (±20%) detector response for non-volatile substances (Eckardt et al. 2018). Dilution series of nine non-volatile CAD reference substances (CAD1-9, concentration range: 1-100 mg/L in DMSO) represented the theoretical detector response corresponding to the calculated TTC thresholds. ...
... Chromatograms were recorded at a wavelength of 242 nm (local UV absorption maximum of TPA) because of the specific UV absorption of the eluent. The 1000-Da limit was determined by using an extract solution of a polybutylene terephthalate (PBT) raw material according to Eckardt et al. (2018). For that purpose, about 50 mg ground PBT pellets were extracted with 2 mL of DCM for 1 h at 60°C in an USB. ...
Article
Coatings for cans or closures are essential to protect the metal from corrosion and the food from migration of hazardous metal ions. Since coatings are no inert materials, they can release substances of potential health concern into food. In the present study, a comprehensive analysis is presented for a complex two-layered polyester–phenol-coating commercially used for metal closures of complementary infant food in sterilised glass jars. Focussed on the identity and migration of cyclic polyester oligomers as a kind of predictable non-intentionally added substances, polyester resin raw materials (n = 3) as well as individual coating layers (n = 3) were characterised by several analytical strategies (size exclusion chromatography, high-performance liquid chromatography mass spectrometry, diode array detection, charged aerosol detection, monomer determination after alkaline hydrolysis, overall migrate). The main polyester monomers were terephthalic acid, isophthalic acid, trimellitic acid, ethylene glycol, diethylene glycol, neopentylglycol, 2-methyl-1,3-propanediol, 1,4-butanediol and tricyclodecanedimethanol. The coatings were extracted with solvents acetonitrile and ethanol (24 h, 60°C), food simulants 50% ethanol, 20% ethanol and water (1 h, 121°C) as well as homemade and commercial baby food (1 h, 121°C). The released total polyester content determined by alkaline hydrolysis ranged from 288 µg/dm² (water, 1 h, 121°C) to 6154 µg/dm² (acetonitrile, 24 h, 60°C). However, individual cyclic oligomers, mainly dimers, were released from the coating to up to about 140 µg/dm². Migration into infant food was best represented by the food simulants water (up to 1% fat) and 20% ethanol (up to 5% fat). Cyclic polyester oligomers are classified as Cramer III substances by the threshold of toxicological concern concept associated to an exposure threshold of 1.5 µg/kg body weight per day. Exposure to cyclic polyester oligomers might be a potential concern for highly exposed infants.
... CAD parameters were set to a power function value (PFV) of 1.2, a noise filter of 5 s and a data collection rate of 25 Hz. The CAD evaporator temperature (EVT) was set either to 35 • C (general measurements) or 50 • C (to determine Q 50/35 value as reported in the literature [18]). Nitrogen (65 psi) was used as nebulization gas. ...
... The Corona CAD is a universal HPLC detector that offers an almost equal response (±20%) for low volatile substances under isocratic elution conditions [18,25,26]. After nebulization and evaporation of the eluent, the surface of the formed analyte particles is loaded with positive nitrogen ions due to a Corona treatment. ...
... An electrometer translates the positive nitrogen charge into a CAD signal, which is proportional to the mass-concentration of the analyte. In the present study, an inverse gradient compensation based on a second gradient pump (IGP) was used to achieve isocratic eluent conditions prior to CAD detection as described in a previous study [18]. The applicability of the CAD universal response quantification approach based on low-volatility can be analytically assessed for any substance by the determination of the Q 50/35 value, representing the CAD response for a substance at two different CAD evaporator temperatures (35 and 50 • C, respectively) [18]. ...
Article
Thermal papers (e.g. point of sale receipts, adhesive labels, tickets) significantly contribute to contamination of paper material cycles and the environment with substances of (eco-) toxicological concern. In particular, they contain color developers like endocrine disrupting bisphenols in typical concentrations of about 1–2 percent per weight (wt%). Bisphenol A (BPA) was used as the common color developer over the last decades, but it will be restricted for thermal paper application in the European Union to a limit of 0.02 wt% from 2020 onwards. Consequently, a variety of BPA substituents such as bisphenol S (BPS) and its derivatives gain importance in thermal paper application. In this study, a rapid, reliable and cost-effective method for identification and quantification of BPA, alternative color developers and related substances like sensitizers is presented based on HPLC separation coupled with diode array detection (DAD) and Corona charged aerosol detection (CAD). Quantification was performed with regard to the intended use of the substances in thermal papers. Besides traditional UV external calibration using reference standards, alternative quantification approaches, in particular UV chromophore concentration for BPS derivatives and CAD universal response technique for low-volatile color developers, were applied and compared in order to allow quantification without reference substances. A market analysis for intended used color developers and sensitizers was performed on thermal paper samples (n = 211) collected in Germany during 2018 and 2019. Pergafast 201 (in 41.7% of the samples) was the most common color developer with concentrations above 0.02 wt%, followed by BPA (36.0%), BPS (13.3%) and other BPS derivatives known as D8, D-90, BPS-MAE and TGSA, that are mainly present in adhesive labels. Sensitizers were determined in over 90% of the samples.
... The uniform response of the CAD for non-volatile analytes has been demonstrated in multiple studies [7,19,20]. Thus, the selection of semi-volatile and non-volatile fatty acids that are structural homologues but differ significantly in their response was essential to develop a model that could accurately predict the CAD response based on a mixed model including the response-determining molecular descriptors. Previous studies on the CAD response of fatty acids revealed a pronounced decline in the response of myristic acid (C14) compared to its structural homologue palmitic acid (C16) [21]. ...
... A significant feature of the so-called universal detectors that justifies their use instead of the commonly applied UV detector, is the minor influence of the physicochemical properties of the analytes on the response. In fact, a relatively uniform response for non-volatile analytes has been demonstrated for the CAD in numerous studies [7,19,20]. However, there might be analyte-related properties influencing the CAD's response at constant experimental settings, such as the density of the compounds, their charge, the hydrogen bond donor capability [41], and the number of electronegative atoms [8]. ...
Article
Full-text available
The charged aerosol detector (CAD) is the latest representative of aerosol-based detectors that generate a response independent of the analytes’ chemical structure. This study was aimed at accurately predicting the CAD response of homologous fatty acids under varying experimental conditions. Fatty acids from C12 to C18 were used as model substances due to semivolatile characterics that caused non-uniform CAD behaviour. Considering both experimental conditions and molecular descriptors, a mixed quantitative structure–property relationship (QSPR) modeling was performed using Gradient Boosted Trees (GBT). The ensemble of 10 decisions trees (learning rate set at 0.55, the maximal depth set at 5, and the sample rate set at 1.0) was able to explain approximately 99% (Q ² : 0.987, RMSE: 0.051) of the observed variance in CAD responses. Validation using an external test compound confirmed the high predictive ability of the model established (R ² : 0.990, RMSEP: 0.050). With respect to the intrinsic attribute selection strategy, GBT used almost all independent variables during model building. Finally, it attributed the highest importance to the power function value, the flow rate of the mobile phase, evaporation temperature, the content of the organic solvent in the mobile phase and the molecular descriptors such as molecular weight (MW), Radial Distribution Function—080/weighted by mass (RDF080m) and average coefficient of the last eigenvector from distance/detour matrix (Ve2_D/Dt). The identification of the factors most relevant to the CAD responsiveness has contributed to a better understanding of the underlying mechanisms of signal generation. An increased CAD response that was obtained for acetone as organic modifier demonstrated its potential to replace the more expensive and environmentally harmful acetonitrile.
... Subsequently, the imposed charge on the particles is measured by a highly sensitive electrometer after removal of excess charge via an ion trap. Hence, the signal output is entirely dependent on the created particles and a nearly universal response depending on the analyte mass is often described [18][19][20][21][22]. According to this operating principle, all substances that behave as semi-and non-volatiles can be assessed with this method. ...
... Some very early studies with inverse gradient compensation were already performed in 2006, just one year after the commercial introduction of the CAD, by Gorecki et al. [100]. More recent studies [18,22,67,[101][102][103] have shown, that the inverse gradient compensation is a valuable tool for generating a rather universal response even in gradient elution mode and hence for quantitation purposes when reference standards are lacking. Furthermore, a drifting baseline due to mobile phase changes can be avoided and stabilized, leading to less noise in the chromatogram, thereby also being beneficial for obtaining better sensitivity. ...
Article
High performance liquid chromatography (HPLC) methods with UV/vis detection are the most widespread analytical procedures in modern pharmaceutical applications, but reach their limitations when it comes to non-chromophore molecules. Hence, instead of using tiresome derivatization procedures, many liquid chromatography methods make use of the so-called aerosol-based universal detectors, namely the evaporative light scattering detector (ELSD), the condensation nucleation light scattering detector (CNLSD) and the charged aerosol detector (CAD). Amongst these, the CAD, being the youngest (introduced in 2005) of these three options, is often described as the most easy-to-use detector and is stated to exhibit sufficient sensitivity and good linearity of signal in a dedicated range of concentration. Therefore, this review sets its focus on the recent applications of the CAD for active pharmaceutical ingredients, excipient analysis as well as botanical applications. Alongside the post-column solvent addition techniques, the new CAD's ability to adjust the evaporation temperature and the possibility to use an integrated power function for signal linearization are reviewed as previously unavailable, new parameters for optimization.
... quantification approaches are mandatory. For homologous UV-active substances such as oligomers from plastics or coating materials the chromophore concentration approach was demonstrated to provide a satisfying quantitative approximation (Schaefer et al. 2004b;Brenz et al. 2018;Eckardt et al. 2018aEckardt et al. , 2018bEckardt et al. , 2020. Briefly, the approach is based on the assumption that the UVresponse of a substance is mainly attributed to the chromophore groups in the structure, e.g. the aromatic (phenolic) rings, rather than to aliphatic substituents. ...
... In summary, the chromophore concentration approach with UV or FL detection can be applied on phenols as a semi-quantitative tool if an availability of standards is limited. However, the range of uncertainty may be considerably greater for phenolic compounds than reported for other homologous oligomers, e.g. from polyester materials (Schaefer et al. 2004b;Eckardt et al. 2018b). ...
Article
Resoles are multifarious pre-polymeric resins produced by the condensation of basic chemicals phenols, formaldehyde and optionally aliphatic alcohols like butanol. They are widely used as cross-linkers to form resistant internal coatings on metal surfaces of cans, containers or closures. Although the application of resoles is common in food contact, usually little is known about their exact composition, the toxicological hazards of their individual constituents and the migration of phenolic compounds, e.g., of the potentially endocrine-disrupting chemical bisphenol F. Our study fills major gaps of knowledge in risk assessment, using the example of a two-layer polyester-phenol coating system, which is based on three different resoles and is commercially used for closures of infant food glass jars. Various analytical approaches, namely size-exclusion chromatography, nuclear magnetic resonance spectroscopy, liquid chromatography coupled to mass spectrometry, fluorescence and diode array detection as well as gas chromatography-mass spectrometry were evaluated to quantitatively characterise resoles. Additionally, derivatisation with dansyl chloride as well as Folin–Ciocalteu colorimetric assay was adapted first times to determine the total phenol content from technical resoles. Individual mono- and bisphenols were determined in resoles up to about 120 mg/g, while the concentration of bisphenol F isomers was below 10 mg/g. Migration from the coating system was determined after sterilisation (121°C, 1 h, 20% ethanol). Results were ~2 µg/dm2 for identified individual mono-phenols like 2-hydroxybenzyl alcohol and up to ~120 µg/dm2 for total phenolic compounds, representing approximately 7% of the overall migration. The migration of bisphenol F isomers was negligible below 0.3 µg/dm2. Potential exposure to migrating phenols was assessed based on the threshold of toxicological concern concept to be significantly below for individual phenols and in the same order of magnitude for total phenols compared to the respective thresholds calculated for infants.
... A few publications that show the applicability of CAD to E&L research; however, none demonstrates the use the CAD to set the AET. A recent application of CAD quantification for E&L was published in 2018 by Eckardt et al. (2018), on the polymer-related, non-intentionally added substances, in polyphenylsulfone (PPSU) used for baby bottles. The authors studied four PPSU raw materials and tested five different in-market baby bottles. ...
... Error bars: standard deviation of triple determination. Reprinted with permission fromEckardt et al. (2018), copyright year 2018 (Taylor & Francis Group, LLC). ...
Article
Full-text available
In addition to degradation products, impurities, and exogenous contaminants, industries such as pharmaceutical, food, and others must concern themselves with leachables. These chemicals can derive from containers and closures or migrate from labels or secondary containers and packaging to make their way into products. Identification and quantification of extractables (potential leachables) and leachables, typically trace level analytes, is a regulatory expectation intended to ensure consumer safety and product fidelity. Mass spectrometry and related techniques have played a significant role in the analysis of extractables and leachables (E&L). This review provides an overview of how mass spectrometry is used for E&L studies, primarily in the context of the pharmaceutical industry. This review includes work flows, examples of how identification and quantification is done, and the importance of orthogonal data from several different detectors. E&L analyses are driven by the need for consumer safety. These studies are expected to expand in existing areas (e.g., food, textiles, toys, etc.) and into new, currently unregulated product areas. Thus, this topic is of interest to audiences beyond just the pharmaceutical and health care industries. Finally, the potential of universal detector approaches used in other areas is suggested as an opportunity to drive E&L research progress in this arguably understudied, under‐published realm.
... The addition of additives to the biopolymers is necessary in order to improve their physico-chemical properties. These additives can be for example: polyols, used as non-volatile plasticizers (e.g., glycerol, glycol, and sorbitol); and resins, that mold the material (e.g., urea, melamine, melamine formaldehyde, and amines) (Eckardt et al., 2018;Geueke, 2013). Surprisingly, melamine and other resins are neither biodegradable or come from natural sources (Chien et al., 2011;Geueke, 2013). ...
Article
New bamboo-based biopolymers are used as food packaging materials, but it must be evaluated to ensure consumers safety. In this study, migration from a commercial bamboo-based biopolymer to ethanol 10% (v/v), acetic acid 3% (w/v) and ethanol 95% (v/v) was studied. The migrants were determined from three different perspectives. Volatile and semi-volatile compounds were analyzed by gas chromatography-mass spectrometry (GC-MS). Twenty-five compounds were detected. In addition, a number of phytosterols were detected in ethanol 95%. Non-volatile compounds were identified and quantified by ultra-performance liquid chromatography coupled to time-of-flight mass spectrometry (UPLC-Q/ToF). Twelve non-volatile compounds were detected in migration solutions, mainly melamine and its derivatives, coming from polymer resins present in the biopolymer. Melamine migration was higher than 50 mg/Kg in the third sequential migration test. Finally, the migration samples were analyzed by DART-SVP (direct analysis in real time coupled to standardized voltage and pressure). This methodology was able to detect simultaneously the main volatile and non-volatile migrants and their adducts in a very rapid and effective way and is shown as a promising tool to test the safety and legal compliance of food packaging materials.
... This is often difficult to verify experimentally and instead is assumed. In this line, the corona charged aerosol detector (CAD) for liquid chromatography has been recently studied as the only detector showing universal response, independent of the analyte, for semi-quantitation of known and unknown non-volatile leachables from linear and cyclic oligomers (Eckardt et al., 2018). For this reason, if a high degree of accuracy is required, semi-quantitation is a less desirable method unless it is sustained by the results of a full validation study. ...
Article
The plastics used in drug packaging systems and medical devices are composed of homologous polymers and generally contain additives such as antioxidants, plasticizers and others, to improve their physicochemical properties. However, these additives have potential drawbacks due to possible migration or leaching towards the drug product. Leaching can cause a change in the chemical composition of the drug which, in turn, could modify its therapeutic action and, in some cases, its organoleptic properties. Leachables may also be considered a health hazard due to their inherent toxicological properties. The analytical characterization (detection, identification, typification/qualification and quantification) of leachable substances is mandatory and this information must be included in the application dossier for the drug before it can receive regulatory approval. The main aim of this paper is to collect and contextualise the reported analytical approaches for characterising and/or controlling organic leachables from plastic materials in contact with drugs. We also describe the state of the art of leachables in conjunction with a valuable, broad-based compilation of directives and guidelines. We end by presenting an updated collection of leachables both gas and liquid chromatography studies as separation techniques over the last eight years. We decided to focus our review exclusively on organic leachables as there is already a wide body of research on inorganic impurities.
... The amount of the analytes electric charge is then measured in the detector cell. Since the CAD is limited to non-volatile analytes above a molecular weight (MW) of approximately 400 g mol −1 [41,42], the mobile phase is restricted to volatile buffers. In addition, CAD response is highly susceptible to the flow rate, the temperature and the compensation of the mobile phase [31,34,43]. ...
Article
Polysialic acid (polySia) is widely investigated in various biopharmaceutical applications (e.g. treatment of inflammatory neurodegenerative diseases), whereby a certain polySia chain length with an average degree of polymerization 20 (polySia avDP20) shows most promising effects. In this study, a rapid analytical method using a HPLC and charged aerosol detector (CAD) for the direct chain length characterization of biopharmaceutically relevant polySia was developed. It was evaluated as a fast alternative to the commonly used 1,2-diamino-4,5-methylenedioxybenzene (DMB) HPLC application. In contrast to HPLC-FLD, the CAD-application provides the actual chain length of polySia within ∼3 h. The reliability of the HPLC-CAD was evaluated with a commercial reference sample of known chain length and biotechnologically produced LC polySia (long chain polySia with a DP ∼130). Moreover, HPLC-CAD was successfully applied in the direct detection of oligo- and polySia until DP ∼65 and can be used to monitor the thermal hydrolysis and subsequent chromatographic isolation of polySia avDP20 (average degree of polymerization 20) without DMB sample derivatization. In addition, CAD was successfully applied for polySia quantification using a modified elution gradient. It was tested as a fast alternative to commonly used thiobarbituric acid (TBA) assay. A differentiation between LC polySia and smaller, hydrolysed polySia chains was intended and possible. For LC polySia and polySia avDP20, a quadratic relation between polySia mass-concentration and CAD signal was observed. In case of LC polySia, a quadratic dependency with a determination coefficient of R2 = 0.99 in a broad concentration range between 0.025 and 15 mg mL−1 was determined. Quantification of polySia avDP20 was found to have quadratic dependency with a determination coefficient of R2 = 0.99 in a concentration range between 0.02 and 0.25 mg mL−1. The HPLC-CAD was tested for quantification with polySia references of known concentration and showed high accordance with a concentration deviation ≤6.7%. The CAD quantification method was also applied in the polySia avDP20 production process and was compared to the TBA assay. Results of a correlation plot showed a high determination coefficient of R2 = 0.98. Overall, HPLC-CAD analysis was successfully tested as a suitable characterization and quantification application in the biopharmaceutical production of polySia.
... polyester oligomers) • Semi-quantification for N-containing substances using a CLND (Nitrogen Chemiluminescence Detector) (Heimrich et al. 2012). • Semi-quantification of non-/semi-volatiles using a CAD (charged aerosol detector) (Eckardt et al. 2018). • Derivatisation of certain substances with an agent with unique UV-chromophore/fluorophore/ MS-fragment (e.g. ...
Article
Full-text available
There are numerous approaches and methodologies for assessing the identity and quantities of non-intentionally added substances (NIAS) in food contact materials (FCMs). They can give different results and it can be difficult to make meaningful comparisons. The initial approach was to attempt to prepare a prescriptive methodology but as this proved impossible; this paper develops guidelines that need to be taken into consideration when assessing NIAS. Different approaches to analysing NIAS in FCMs are reviewed and compared. The approaches for preparing the sample for analysis, recommended procedures for screening, identification, and quantification of NIAS as well as the reporting requirements are outlined. Different analytical equipment and procedures are compared. Limitations of today's capabilities are raised along with some research needs.
... All chromatographic methods were validated in terms of limit of detection (LOD), limit of quantification (LOQ), % relative standards deviation (RSD), and correlation coefficient, see Table 5. For the analysis of oligomers and unknown compounds, proxy standards including BHET, BADGE, and BADGE.2H 2 O were used for polyesters, epoxy, and acrylic-phenolic coatings, respectively, as it was suggested elsewhere [34,[36][37][38][39]. ...
Article
Full-text available
In this study, an accelerated migration test on food can coatings into food simulants was investigated. Food simulants covering a wide range of polarity were used to conduct migration tests at 60 °C with storage times ranging from 4 h to 30 days. Epoxy-resins, acrylic–phenolic, polyester, and vinyl coatings were exposed to water, 3% acetic acid, 50% ethanol, and Miglyol 812®. Using liquid chromatography coupled to a variety of detectors (UHPLC-Q-Orbitrap-MS, UFLC-MS/MS, and HPLC-DAD), migration of several monomers and previously identified oligomers, as well as some unidentified migrants, were determined during the experiment. The data from this study was compared to our findings from previous long-term migration studies with storage times ranging from 24 h to 540 days at 40 °C using the same can coating applications. The results illustrate that performing migration experiments for short time periods at 60 °C may mimic migration results that would be obtained at 40 °C after long-term migration tests (up to 1.5 years) from food can coatings into food simulants.
... Pelleted PET and PBT polyester materials in foodgrade quality were obtained from industrial partners. Individual cyclic oligomers from PET (trimer, PET-C 3+3 , see Figure 1) as well as from PBT (dimer, PBT-C 2+2 and trimer, PBT-C 3+3 , see Figure 1) were isolated and purified from the extracted raw material pellets as described elsewhere (Eckardt et al. 2018). The purities were >98%, determined via HPLC-UV 242nm and charged-aerosol detection (CAD). ...
Article
Linear and cyclic oligomers are unavoidable non-intentionally added substances (NIAS) present in food contact materials made from common polyesters such as polyethylene terephthalate (PET), polybutylene terephthalate (PBT) and polyester coatings. Although polyester oligomers can migrate into fats in significant amounts in high-temperature processes such as baking or frying, little is known about their toxicological properties and their behaviour in the human gastrointestinal tract. In the present study, first indications of a possible digestibility of polyester oligomers formed from the commonly used aromatic dicarboxylic acid terephthalic acid (TPA) are provided by in vitro experiments. Three cyclic polyester oligomers originated from PET (trimer) and PBT (dimer and trimer) were extracted from the raw materials, isolated and subjected to a simulated intestinal digestion. A fast cleavage (≥75% of the initial amount) of all three cyclic oligomers into their linear counterparts was detected already within the first hour of in vitro intestinal incubation. Subsequent hydrolysis to shorter chained linear oligomers was determined especially for the PET cyclic trimer. Degradation down to the monomer TPA was not observed. In terms of risk assessment and prioritisation for non-evaluated NIAS, the threshold of toxicological concern (TTC) concept is an appropriate tool. While cyclic polyester oligomers based on TPA are assigned to the TTC Cramer class III (high potential concern, exposure threshold 1.5 µg/kg body weight per day), the corresponding linear oligomers are expected to be of a lower probable toxicological concern (Cramer class I, 30 µg/kg body weight per day). A cleavage of cyclic polyester oligomers under human intestinal conditions, which was assessed to be likely by the provided in vitro experiments, could consequently affect the risk assessment on polyester oligomers.
... These substances have been found in food-grade PET, in particular the 1st series cyclic PET dimer and trimer, and the 2nd and 3rd series cyclic dimers (Table 1). They have been quantified in both vPET and rPET FCMs, and their use as an indicator of the PET production history has been suggested (Alberto Lopes et al., 2021a;Eckardt et al., 2018;Hoppe et al., 2017;van Velzen et al., 2020;Tsochatzis et al., 2020;Ubeda et al., 2018). ...
Article
Polyethylene terephthalate (PET) is a polymer deemed safe to be mechanically recycled and used in food contact applications. Its recycled form (rPET) can be used as a food contact material (FCM). Although this is an obvious positive step towards a more circular economy, the development of an appropriate analytical toolbox to experimentally assess and evaluate the various steps during end of life and mechanical recycling is still at its infancy. The safety of the decontamination process is currently evaluated following a conventional modelling approach applied to a specific number of compounds (challenge test). However, additional compounds, quality markers and process controls are needed, with respect to migrating substances, potential non-intentionally added substances (NIAS), contaminants and known polymeric degrading compounds. This would ensure an additional level of safety and provide recomendations for the application of appropriate methods when ensuring full compliance with safety standards for rPET. This review presents the current regulatory framework and the most recent developments in analytical methodologies related to compliance testing. It also highlights some of most described chemical substances found in food-grade rPET.
... Efforts have been made into combating this effect by eluent compensation for both ELSD and CAD, where the eluent is adjusted after separation but before detection to keep the eluent composition entering the detector constant [3,4]. This approach was used by Eckardt et al. to quantify oligomers extracted from a variety of polymers with the CAD [70]. By use of universal response-based quantification, a variety of oligomers could be quantified, a variation in the response factor of ± 20% was found between different oligomers. ...
Article
Full-text available
Accurate quantification of polymer distributions is one of the main challenges in polymer analysis by LC. The response of contemporary detectors is typically influenced by compositional features such as molecular weight, chain composition, end groups and branching. This renders the accurate quantification of complex polymers of which there are no standards available, extremely challenging. Moreover, any (programmed) change in mobile-phase composition may further limit the applicability of detection techniques. Current methods often rely on refractive index detection, which is not accurate when dealing with complex samples as the refractive-index increment is often unknown. We review current and emerging detection methods in liquid chromatography with the aim of identifying detectors which can be applied to the quantitative analysis of complex polymers. This article is protected by copyright. All rights reserved.
... Non-volatile oligomers were shown to be semiquantifiable by HPLC coupled to CAD as the detector response is almost equal for non-volatile substances independent on their chemical structure at constant eluent composition (Eckardt et al. 2018). A quotient of substance peak areas at CAD evaporator temperatures at 50°C by 35°C (Q 50/35 ) was used as an indicator of volatility; non-volatile substances possess a Q 50/35 of at least 0.85. ...
Article
Styrene-acrylonitrile-copolymer (SAN) and acrylonitrile-butadiene-styrene-copolymer (ABS) are gaining in importance as food contact materials. Oligomers and other non-intentionally added substances can migrate into foodstuffs. Five SAN and four ABS samples from the German market and manufacturers were extracted and the extractable oligomers were characterised by high performance liquid chromatography-mass spectrometry/ultraviolet detection/chemiluminescence nitrogen detection/fluorescence detection and gas chromatography-mass spectrometry. Trimers, formed from acrylonitrile and styrene units, were determined to be the dominating group of extractable oligomers in SAN and ABS in concentrations of about 4900–15800 mg/kg material. Furthermore, styrene-acrylonitrile dimers, styrene oligomers, styrene monomer and ethylbenzene were identified in the sample extracts. Migration testing with three consecutive migrations for multiple use articles was performed for two SAN articles. Migration of trimers into water, 3% acetic acid, 10% and 20% ethanol under hot-fill conditions (70°C, 2 h) was not detectable above 9 µg/dm², while 50% ethanol acting as a food simulant for milk (124 µg/dm² trimers during the third migration) was shown to overestimate the actual migration into milk (< 11 µg/dm² trimers at 70°C, 2 h). 2-Amino-3-methyl-1-naphthalenecarbonitrile (AMNC), an oligomer degradation product and a primary aromatic amine, was detected in all material sample extracts (0.3–17.1 mg/kg material) and was released into food simulants in low amounts (< 0.014 µg/dm² during the third migration into 50% ethanol at 70°C, 2 h).
Article
Polyester yarn is successfully dyed with disperse dye in a low-pressure non-aqueous medium dyeing system. However, oligomers with different low molecular mass are formed during manufacture of polyesters, which can diffuse into the dyeing bath or be adsorbed on the dyeing machine during dyeing process. In this investigation, oligomers of different polyester yarns were extracted with tetrachloroethane solution, and analyzed using Fourier transform infrared spectroscopy (FTIR), proton nuclear magnetic resonance (NMR), thermogravimetric analysis (TGA), high performance liquid chromatography (HPLC), and liquid chromatography-mass spectrometry (LCMS). The amount of oligomer that was isolated by reprecipitation method ranged from 1.83 % to 4.07 % (on the weight of yarn) in the respective yarn, and more than 80 % of the components are cyclic oligomers. The thermal profile of oligomer showed it had a faster weight loss at 183 °C and 470 °C which was compared with polyester (473 °C). HPLC and LC-MS analysis results further indicated that 99 % of the oligomers were cyclic trimers during dyeing. Moreover, the dyeing color depth of dyed yarn and the uptake of dye would be greatly improved after the oligomer of polyester yarn was removed. Otherwise, the oligomer may affect the color fastness and levelness of the dyed polyester samples.
Article
In terms of risk assessment especially for the impurities with different ultraviolet (UV) absorptions in 16-membered macrolides produced by fermentation, quantification without the availability of corresponding reference substances currently poses a challenge. In this study, a reliable method was established for the analysis of impurities in 16-membered macrolides for the first time by high performance liquid chromatography tandem with charged aerosol detector (HPLC-CAD). The chromatographic conditions and CAD parameters were optimized for a good separation and sensitivity. The impurities were identified by ion trap time-of-flight mass spectrometry (IT-TOF/MS), the developed method was validated, and the sources of degradation impurities in production were investigated. Based on the experimental results, the superiority of the developed method over UV detection was demonstrated that the method provided a universal response to impurities with differences chromophores. In the method validation, good linearity was obtained with coefficient of determination (R2) greater than 0.999 in the range of 2-100 μg·mL-1. The limit of detection (LOD) and limit of quantification (LOQ) were 5 and 15 ng for impurity Ⅲ, respectively. The average content of the impurity Ⅲ was found to be 0.4 % in leucomycin. The recoveries were 98.7 %-102.5 % at the spiked concentration levels of 0.40 %, 0.60 % and 0.80 % with relative standard deviations (RSDs, n=3) lower than 2.0 %. The impurities in 10 leucomycin samples were determined to be 3.2 %-5.2 %. Finally, the acidity of solution during the purification and the temperature of drying process were found to be the main factors that causing the increased amount of impurities. Overall, the developed HPLC-CAD quantification method was a suitable alternative for the analysis of impurities in the 16-membered macrolides discussed in this manuscript. Our study provided guidance for pharmaceutical companies to improve the manufacturing process and control the impurities.
Thesis
Liquid chromatography has become the gold standard for modern quality control and purity analytics since its establishment in the 1930s. However, some analytical questions remain very challenging even today. Several molecules and impurities do not possess a suitable chromophore for the application of UV detection or cannot be retained well on regular RP columns. Possible solutions are found in derivatization procedures, but they are time consuming and can be prone to errors. In order to detect non chromophore molecules underivatized, the concept of aerosol based universal detection was established with the introduction of the evaporative light scattering detector (ELSD) in the 1970s and the charged aerosol detector (CAD) followed in 2002. These two challenging fields – polar and non chromophore molecules – are tackled in this thesis. An overview of applications of the CAD in the literature and a comparison to its aerosol based competitors and MS is presented, emphasizing on its high sensitivity and robustness. Parameters and techniques to overcome the drawbacks of CAD, such as the use of gradient compensation or adjusted evaporation temperatures are discussed. A consideration of aspects and drawbacks of data transformation such as the integrated power function value (PFV) in the GMP environment is performed. A method for the fatty acid analysis in polysorbate 80 that was developed on HPLC CAD was transferred to UHPLC CAD. Time and eluent savings of over 75% and 40%, respectively, as well as ways to determine the optimal CAD parameters resulted from this investigation. The evaporation temperature was determined as the most crucial setting, which has to be adjusted with care. Optimal signal to noise ratios are found at a compromise between maintaining analyte signal and reducing background noise. The incorporation of semi volatile short chain fatty acids enabled the observation of differences based on volatility of the analyte. E.g. for semi volatiles, an improved linearity by means of adjusting the PFV is achieved at values below 1.0 instead of at elevated PFVs. Using sugars and sugar related antibiotics, a proof-of-concept was given that artificial neural networks can describe correlations between the structure and physicochemical properties of molecules and their response in CAD. Quantitative structure property relationships obtained by design of experiment approaches were able to predict the response of unseen substances and yielded insights on the response generation of the detector, which heavily relies on the formed surface area of the dried particle. Further work can substantiate upon these findings, eventually building a library of diverse eluent compositions, analytes and settings. In order to cope with a chromatographically challenging substances, the application of ion pairing reversed phase chromatography coupled to low wavelength UV detection has been shown as a possible approach for the amino acid L asparagine. A method capable of compendial purity analysis in one single HPLC approach, thus making the utilization of the semi quantitative TLC-ninhydrin analysis obsolete, resulted from this. One cyclic dipeptide impurity (diketoasparagine) that was formerly not assessed, could be identified in several batches and added to the monograph of the Ph.Eur. Studying ibandronate sodium with CAD and ELSD, it was found that randomly occurring spike peaks represent a major flaw of the ELSD when high sample load is present. The research with this non chromophore bisphosphonate drug furthermore shed light on possible drawbacks of mixed mode chromatography methods and ways to overcome these issues. Due to strong adsorption of the analyte onto the column, over ten injections of the highly concentrated test solution were found to be necessary to ensure reproducible peak areas. Preconditioning steps should thus be evaluated for mixed mode approaches during method development and validation. Last, using a ternary mixed mode stationary phase coupled to CAD, a method for the impurity profiling of pamidronate disodium, also applicable to the assessment of phosphate and phosphite in four other bisphosphonate drugs, has been developed. This represents a major advantage over the Ph.Eur. impurity profiling of pamidronate, which requires two different methods, one of which is only a semi quantitative TLC approach.
Thesis
The charged aerosol detector (CAD) is an aerosol-based detector employed in liquid chromatography which has become established in the field of pharmaceutical analysis due to its outstanding performance characteristics, e.g. the almost uniform response for nonvolatile analytes. Owing to its principle of detection, the response of the CAD depends on the volatility of a compound and is inherently nonlinear. However, the newly implemented instrumental settings evaporation temperature and power function value (PFV) are valuable tools to overcome some of these drawbacks and can even enhance the detector’s capabilities when adjusted properly. This thesis aimed to evaluate the impact of the new instrumental settings on the CAD performance. Additionally, the influence of modern separation techniques for small polar compounds on the CAD was assessed and the applicability of hyphenated UV-CAD techniques explored. The optimization strategies derived from the evaluation procedures and the conjunction of the instrumental and chromatographic techniques investigated were utilized for the challenging impurity profiling of amino acids and amino acid-like drugs. The results of the method validation procedures confirmed the broad applicability of the CAD in the pharmaceutical analysis of nonvolatile compounds, supported by satisfactory sensitivity and reproducibility for meeting the regulatory requirements with respect to the ICH guidelines Q2(R1) and Q3A(R2). The limits of applicability include the analysis of semivolatile compounds, and the method transfer between current and legacy CAD models. Further advances in the definition and standardization of allowed ranges for the instrumental settings and the establishment of general optimization procedures in the method development could lead to a more widespread use of the detection technique in compendial methods.
Article
Polysaccharides from natural medicines, being safe and effective natural mixtures, show great potential to be developed into botanical drugs. However, there is yet one polysaccharide-based case that has fulfilled the Botanical Guidance definition of a botanical drug product. One of the reasons is the analytical methods commonly used for qualitative and quantitative analysis of polysaccharides fall far behind the quality control criteria of botanical drugs. Here we systemically reviewed the recent advances in analytical methods. A critical evaluation of the strength and weaknesses of these methods was provided, together with possible solutions to the difficulties. Mass spectrometry with or without robust chromatographic separation was increasingly employed. And scientists have made significant progress in simplifying polysaccharide quantification by depolymerizing it into oligosaccharides. This oligosaccharides-based strategy is promising for qualitative and quantitative analysis of polysaccharides. And continuous efforts are still needed to develop a standardized quality control method that is specific, accurate, repeatable, and applicable for analyzing individual components in natural medicine formulas.
Article
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Fermentable oligo-, di-, and monosaccharides and polyols (FODMAPs) are associated with digestive disorders and with diseases such as irritable bowel syndrome. In this study, we determined the FODMAP contents of bread, bakery products, and flour and assessed the effectiveness of sourdough fermentation for FODMAP reduction. The fermentation products were analyzed to determine the DP 2–7 and DP >7 fructooligosaccharide (FOS) content of rye and wheat sourdoughs. FOSs were reduced by Acetobacter cerevisiae, Acetobacter okinawensis, Fructilactobacillus sanfranciscensis, and Leuconostoc citreum to levels below those in rye (−81%; −97%) and wheat (−90%; −76%) flours. The fermentation temperature influenced the sourdough acetic acid to lactic acid ratios (4:1 at 4 °C; 1:1 at 10 °C). The rye sourdough contained high levels of beneficial arabinose (28.92 g/kg) and mannitol (20.82 g/kg). Our study contributes in-depth knowledge of low-temperature sourdough fermentation in terms of effective FODMAP reduction and concurrent production of desirable fermentation byproducts.
Article
Toxic impurities were found in leucomycin and its preparation, however the content determination of impurities was challengeable due to the lacking of their reference standards. In this study, we developed high-performance liquid chromatography method coupled with charged aerosol detection (CAD) for the quantification of related substance of leucomycin (kitasamycin) bulk drugs and tablets, however, the CAD was not yet popular. In order to carry out quantitation work conveniently in the laboratory without CAD instruments, a high-performance liquid chromatography method coupled with ultraviolet (UV) detection was developed with the assistant of the HPLC-CAD results. The relative response of impurities on CAD chromatogram was used for guiding the establishment of HPLC-UV method, which could achieve the quantitation task in the absence of impurity reference standards. The developed HPLC-UV method was validated according to the ICH guideline and showed good precision, reproducibility and linearity with determination coefficient higher than 0.9999. The limit of detection and quantitation were 0.3 and 0.5 μg mL⁻¹, respectively. The recoveries were 92.9 %–101.5 % at the spiked concentration levels of 0.1%, 0.8 %, 1.0 and 1.2 % with relative standard deviations (RSDs, n = 3) lower than 2.0 %. Finally, the developed HPLC-CAD and -UV methods were compared by the determination of impurities in several batches of leucomycin bulk drugs and tablets. The results demonstrated that the developed HPLC-UV method was simple and reliable. This study developed methods to quantify the related substance in leucomycin and tablets, and discussed a strategy of the conversion of HPLC-CAD method to HPLC-UV method. The developed methods could be considered for implementation into pharmacopeial monographs in the future.
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Several food contact materials (FCMs) contain non-intentionally added substances (NIAS), and most of the substances that migrate from plastic food packaging are unknown. This review aimed to situate the main challenges involving unknown NIAS in plastic food packaging in terms of identification, migration tests, prediction, sample preparation, determination methods and risk assessment trials. Most studies have identified NIAS in plastic materials as polyurethane adhesives (PU), polyethylene terephthalate (PET), polyester coatings, polypropylene materials (PP), multilayers materials, plastic films, polyvinyl chloride (PVC), recycled materials, high-density polyethylene (HDPE) and low-density polyethylene (LDPE). Degradation products are almost the primary source of NIAS in plastic FCMs, most from antioxidants as Irganox 1010 and Irgafos 168, following by oligomers and side reaction products. The NIAS assessment in plastics FCMs is usually made by migration tests under worst-case conditions using food simulants. For predicted NIAS, targeted analytical methods are applied using GC-MS based methods for volatile NIAS and GC-MS and LC-MS based methods for semi- and non-volatile NIAS; non-targeted methods to analyze unknown NIAS in plastic FCMs are applied using GC and LC techniques combined with QTOF mass spectrometry (HRMS). In terms of NIAS risk assessment and prioritization, the threshold of toxicological concern (TTC) concept is the most applied tool for risk assessment. Bioassays with sensitive analytical techniques seem to be an efficient method to identify NIAS and their hazard to human exposure; the combination of genotoxicity testing with analytical chemistry could allow the Cramer class III TTC application to prioritize unknown NIAS. The scientific justification for implementing a molecular weight-based cut-off (
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There is a great need for efficient analysis of the composition of vegetable oils and fats, since it affects the physical and technical properties. However, due to the complex nature of these kind of samples, it is often difficult and costly. In the present study, we developed a Non-Aqueous Reversed-Phase HPLC method that can be used to separate and quantify different free fatty acids, fatty acid esters, monoacylglycerides, diacylglycerides and triacylglycerides, including regioisomers such as SOS/SSO and 1,2- and 1,3-diolein. Two 25 cm Nucleodur C18 Isis columns in series, sub-ambient column temperature and a mobile phase gradient composed of acetonitrile, acetic acid, isopropanol and heptane were used for the separation. The lipids were detected and quantified using a charged aerosol detector and it was found that the peak shape highly affected the detector response as well as the response uniformity, even when inverse gradient compensation was employed. Thus, calibration and determination of response factors were necessary for reliable quantification. A correlation between response factors and peak width at half peak height was found and used for quantification of non-calibrated components. A quantification approach was suggested including an appropriate selection of calibrated components, depending on sample composition and the accuracy required. It was shown in a complex oil sample that the reduced calibration approach, using only 6 instead of 33 calibrated components, resulted in virtually the same composition, but yielded a more accurate result compared to using relative area that neglects response factors. The method validation showed good reproducibility and accuracy, making it an excellent tool for extensive analysis of complex lipid mixtures.
Article
The charged aerosol detector (CAD) is frequently employed in liquid chromatography for the analysis of small polar and ionizable compounds such as amino acids and amino sugars, which provide a weak chromophore only. Separation of these compounds is achieved by means of ion pair chromatography (IPC), and, more recently, hydrophilic interaction chromatography (HILIC) techniques. However, as the CAD's response is highly dependent on the mobile phase composition, the substantial differences in the mobile phase composition of IPC and HILIC have a distinct impact on the detector's performance. This study was aimed at systematically comparing the performance of IPC and HILIC when coupled to the CAD. Therefore, the separation techniques characterized by their specific mobile phase compositions were evaluated for their influence on the CAD response and the signal-to-noise ratio (S/N) of the amino acids L-alanine, L-leucine, and L-phenylalanine applying the response surface methodology (RSM). The RSM results derived from flow injection analysis (FIA) indicated that the CAD response and thus the obtainable S/N are significantly higher in HILIC compared to IPC where the S/N decreased with the chain length of the applied ion-pairing reagent. In addition, an IPC and a HILIC method, respectively, were developed for the impurity profiling of the branched-chain amino acids (BCAAs) L-leucine, L-isoleucine, and L-valine. The beneficial effects of the HILIC conditions on the S/N observed under FIA conditions were partly offset by moderate column bleed effects when using an amide functionalized column, which facilitates the separation in the HILIC method. Satisfactory LOQs (3-10 ng on column) were obtained with both methods; however, the HILIC method was found to be slightly superior in terms of sensitivity and separation efficiency.
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In recent years, the use of quantitative liquid chromatography (LC) coupled charged aerosol detection (CAD) for poor UV absorbing analytes in multicomponent mixtures has grown exponentially across academic and industrial sectors. The ballpark of previous LC-CAD reports is focused on practical applications, as well as optimization of critical parameters such as: response dependencies on temperature, nebulization process, analyte volatility, and mobile-phase composition. However, straightforward approaches to deal with the characteristic nonlinear response of CAD still scarce. A highly overlooked parameter is the power function value (PFV), whose optimization enables a detection signal that is more linear with higher signal-to-noise ratio (S/N) and lower relative standard deviation (RSD) of area counts. Herein, a systematic investigation of different regression models (log-log, first-and second-degree polynomial) by both interpolation and extrapolation process in conjunction with PFV optimization throughout the development of LC-CAD assays is reported. The accuracy of the results via interpolation is always good (< 5%) when operating in the vicinity of the optimum PFV regardless the regression model choice. On the contrary, extrapolation process only worked when applying log-log regression at the optimum PFV (accuracy <5%). This outcome indicates that a first-order regression via interpolation can be a safe and simple choice for quantitative LC-CAD in highly regulated laboratories (GLP, GMP, etc.). Whereas a straightforward extrapolation combined with log-log regression can enable the deployment of high-throughput LC-CAD assays, especially but not limited to laboratories where the synthetic process route is undergoing rapid change and optimization (medicinal chemistry, discovery, biocatalysis, process chemistry, etc.). This approach is crucial in developing quantitative LC-CAD assays for poor UV absorbing pharmaceuticals that are sensitive, precise, accurate and robust across early and late-stage pharmaceutical development.
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FDA guidance for food contact substances recommends that for food packaging intended for use at sterilized, high temperature processed or retorted conditions, a migration test with a retort step at 121 ºC for 2 hours follow by 10 days migration test at 40 ºC should be performed. These conditions are in intended to simulate processing and long term storage, however, can coatings may be in contact with food for years and there is very little data evaluating if this short term testing accurately simulate migration over extended time periods. A long term migration test at 40 ºC with retorted and non-retorted polyester cans using several food simulants (water, 3% acetic acid, 10% ethanol, 50% ethanol and isooctane) was conducted to verify whether traditional migration testing protocols accurately predict migration from food contact materials used for extended time periods. Time points were from 1 day to 515 days. HPLC-MS/MS was used to analyze polyester monomers and oligomer migration was monitored using HPLC-DAD/CAD and HPLC-MS. Concentration of monomers and oligomers increased during the migration experiments especially in ethanol food simulants. The data suggests that current FDA migration protocols may need to be modified to address long term storage conditions.
Article
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The performance of the charged aerosol detector (CAD) was investigated using a diverse set of 29 solutes, including acids, bases and neutrals, over a range of mobile phase compositions, particularly with regard to its suitability for use in hydrophilic interaction chromatography (HILIC). Flow injection analysis was employed as a rapid method to study detector performance. CAD response was ‘quasi-universal’, strong signals were observed for compounds that have low volatility at typical operating (room) temperature. For relatively involatile solutes, response was reasonably independent of solute chemistry, giving variation of 12-18% rsd from buffered 95% ACN (HILIC) to 10% ACN (RP). Somewhat higher response was obtained for basic compared with neutral solutes. For cationic basic solutes, use of anionic reagents of increasing size in the mobile phase (formic, trifluoroacetic and heptafluorobutyric acid) produced somewhat increased detector response, suggesting that salt formation with these reagents is contributory. However, the increase was not stoichiometric, pointing to a complex mechanism. In general, CAD response increased as the concentration of acetonitrile in the mobile phase was increased from highly aqueous (10% ACN) to values typical in the HILIC range (80-95% ACN), with signal to noise ratios about 4 times higher than those for the RP range. The response of the CAD is non-linear. Equations describing aerosol formation cannot entirely explain the shape of the plots. Limits of detection (determined with a column for solutes of low k) under HILIC conditions were of the order of 1-3 ng on column, which compares favourably with other universal detectors. CAD response to inorganic anions allows observation of the independent movement through the column of the cationic and anionic constituents of basic drugs.
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The US Food and Drug Administration's Office of Food Additive Safety in the Center for Food Safety and Applied Nutrition conducts safety assessments of food additives, including food-contact substances such as polymeric and oligomeric materials that have the potential to migrate to food. Traditionally, little toxicity testing has been conducted on the low-molecular weight oligomeric fraction (< 1000 Da) of these food-contact substances. At lower exposures (≤ 150 μg/person/day), safety has been assessed based on the use of toxicity data on the monomeric components of these polymers as a sufficiently conservative approach for addressing the concern for genetic toxicity and carcinogenicity of the low-molecular weight oligomers (LMWOs). This paper discusses this assumption relative to the available data on these substances and their monomeric components in the context of exposures of ≤ 150 μg/person/day with emphasis on the evaluation of the potential genetic toxicity of these compounds. In most instances, data are available on either the monomers or the monomers' structural class to conservatively address the potential genetic toxicity of the LMWOs. Caveats to this generalization are also discussed. The assessment of LMWOs is important because they can be one of the primary migrants to food from a polymeric food-contact substance.
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Unknown substances, not previously observed, are frequently detected in foods by quality control laboratories. In many cases, the assessment of these 'new' substances requires additional chemical analysis for their identification prior to assessing risk. This identification procedure can be time-consuming, expensive and in some instances difficult. Furthermore, in many cases, no toxicological information will be available for the substance. Therefore, there is a need to develop pragmatic tools for the assessment of the potential toxicity of substances with unknown identity to avoid delays in their risk assessment. Hence, the 'ILSI Europe expert group on the application of the threshold of toxicological concern (TTC) to unexpected peaks found in food' was established to explore whether the TTC concept may enable a more pragmatic risk assessment of unknown substances that were not previously detected in food. A step-wise approach is introduced that uses expert judgement on the source of the food, information on the analytical techniques, the dietary consumption of food sources containing the unknown substance and quantitative information of the unknown substance to assess the safety to the consumer using the TTC. By following this step-wise approach, it may be possible to apply a TTC threshold of 90 μg/day for an unknown substance in food.
Article
Polyphenylsulfone (PPSU) is a new material for the production of baby bottles. PPSU is a polyether plastic formally composed of bisphenol S (BPS) and 4,4ʹ-dihydroxybiphenyl (DHBP), which both have slight endocrine activities in in-vitro-tests. So far, little is known about the presence and the release of potentially hazardous substances from PPSU baby bottles. In our present study, we present a three step approach for the analysis of PPSU starting with polymer characterization in terms of chemical structure, total oligomer content and hydrolytic stability. Second is the determination of extractables focussing on monomers, monomer derivatives, linear and cyclic oligomers below 1000 dalton (Da) and residual solvent. Third is a risk assessment on migration-related substances in accordance to EU plastics regulation No 10/2011 based on triplicate consecutive migration experiments using official milk simulant 50% ethanol. We analysed five types of PPSU baby bottles from different brands as well as corresponding raw materials from different manufacturers by various analytical techniques (HPLC-DAD/FLD/Corona/ESI-MS, HPLC-SEC, GC-MS, ¹H-NMR). We found significant variations of PPSU materials from different producers with regard to polymer and oligomer chain end groups (methoxylation, chlorination), while total oligomer content below 1000 Da was similar (mean about 0.48%). BPS was not detected above 0.3 mg/kg polymer in any PPSU sample. Residual DHBP content ranged between 1.7 and 15.5 mg/kg polymer. The most common oligomer in all PPSU samples was the cyclic tetramer (about 1200 mg/kg polymer), which is the only cyclic compound below 1000 Da. Residual solvent, sulfolane, was determined to a maximum of 1300 mg/kg polymer. In migration tests, we detected exceedances of neither specific migration limits (SML) for listed substances nor of thresholds of toxicological concern (TTC) for non-listed substances (monomer derivatives, oligomers). Based on our analytical results, no concerns exist regarding migration of polymer-related substances from PPSU baby bottles.
Article
Polybutylene terephthalate (PBT) is a polyester (PES) gaining more importance on the food contact material (FCM) market. However, little is known about the potential migration of PBT oligomers which are formed during the polymer production. In this work, PBT pellets and a slotted spoon manufactured from this material by injection moulding were analysed on extractable oligomers and their migration potential into hydrophilic foods. Overall 27 oligomers (cycles and linears) could be identified in different extracts by HPLC-DAD/ESI-MS data, but without confirmation by reference substances. The oligomers were quantified by HPLC-DAD using bis(2-hydroxyethyl) terephthalate (BHET) as external standard and the total amount of oligomers isolated by reprecipitation from the pellets and the spoon were 0.69 and 0.71 %, respectively. While cyclic oligomers made up for approx. 90 % of the extractable oligomers, linear oligomers proved to be more relevant for migration into aqueous foodstuffs. Furthermore, it was shown that hydrolysis of oligomers can take place in water at elevated temperatures. Consequently, the qualitative and quantitative composition of PBT oligomers in aqueous foods from FCMs does not only depend on migration but also on hydrolysis. Migration testing of the PBT spoon under repeat use conditions with water at 100 °C for 2 h resulted in 0.29 mg item⁻¹ of linear oligomers and 0.05 mg item⁻¹ of the cyclic PBT dimer in the third migrate.
Article
Universal quantitative detection without the need for analyte reference standards would offer substantial benefits in many areas of analytical science. The quantitative capability of high performance liquid chromatography (HPLC) with charged aerosol detection (CAD) was investigated for 50 compounds with a wide range of physical and chemical properties. It is widely believed that CAD is a mass detector. Quantification of the 50 compounds using a generic calibrant and mass calibration achieved an average error of 11.4% relative to 1H NMR. Correction factors are proposed that estimate the relative surface area of particles in the detector, taking into account the effects of the density and charge of analytes. Performing these corrections and quantifying with surface area calibration, rather than mass, shows considerably improved linearity and uniformity of detection, reducing the average error relative to 1H NMR to 7.1%. The accuracy of CAD quantification was most significantly improved for highly dense compounds, with traditional mass calibration showing an average error of 34.7% and the newly proposed surface area calibration showing an average error of 5.8%.
Article
Polyesters (PES) are gaining more importance on the food contact material (FCM) market and the variety of properties and applications is expected to be wide. In order to acquire the desired properties manufacturers can combine several FCM approved polyvalent carboxylic acids (PCA) and polyols as monomers. However, information about the qualitative and quantitative composition of FCM articles is often limited. The method presented here describes analysis of PES with the identification and quantification of 25 polyester monomers (10 PCA, 15 polyols) by HPLC with diode array detection (HPLC-DAD) and GC-MS after alkaline hydrolysis. Accurate identification and quantification was demonstrated by the analysis of seven different FCM articles made of PES. The results explained between 97.2 and 103.4 % w/w of the polymer composition whilst showing equal molar amounts of PCA and polyols. Quantification proved to be precise and sensitive with coefficients of variation (CV) below 6.0 % for PES samples with monomer concentrations typically ranging from 0.02 to 75 % w/w. The analysis of 15 PES samples for the FCM market revealed the presence of 5 different PCA and 11 different polyols (main monomers, co-monomers, non-intentionally added substances (NIAS)) showing the wide variety of monomers in modern PES. The presented method provides a useful tool for commercial, state and research laboratories as well as for producers and distributors facing the task of FCM risk assessment. It can be applied for the identification and quantification of migrating monomers and the prediction of oligomer compositions from the identified monomers, respectively.
Article
p>Synthetic and naturally occurring substances present in food and feed, together with their possible breakdown or reaction products, represent a large number of substances, many of which require risk assessment. EFSA’s Scientific Committee was requested to evaluate the threshold of toxicological concern (TTC) approach as a tool for providing scientific advice about possible human health risks from low level exposures, its applicability to EFSA’s work, and to advise on any additional data that might be needed to strengthen the underlying basis of the TTC approach. The Scientific Committee examined the published literature on the TTC approach, undertook its own analyses and commissioned an in silico investigation of the databases underpinning the TTC approach. The Scientific Committee concluded that the TTC approach can be recommended as a useful screening tool either for priority setting or for deciding whether exposure to a substance is so low that the probability of adverse health effects is low and that no further data are necessary. The following human exposure threshold values are sufficiently conservative to be used in EFSA’s work; 0.15 μg/person per day for substances with a structural alert for genotoxicity, 18 μg/person per day for organophosphate and carbamate substances with anti-cholinesterase activity, 90 μg/person per day for Cramer Class III and Cramer Class II substances, and 1800 μg/person per day for Cramer Class I substances, but for application to all groups in the population, these values should be expressed in terms of body weight, i.e. 0.0025, 0.3, 1.5 and 30 μg/kg body weight per day, respectively. Use of the TTC approach for infants under the age of 6 months, with immature metabolic and excretory systems, should be considered on a case-by-case basis. The Committee defined a number of exclusion categories of substances for which the TTC approach would not be used.</p
Article
Background: Over the last years the variety of food and beverage packaging has increased with the development of new plastic materials and (co)polymer modifications. Oligomers which are always present in polymers evoke attention as potential migrants, from a qualitatively and quantitatively viewpoint. Scope and approach: This article deals with oligomers as potential migrants from plastics food contact materials and reviews their occurrence as well as analytical methods for their identification and quantification. Additionally a section about migration summarizes literature providing oligomer levels in food simulants and foods. Special attention was given to polycondensates since these represent a rapidly expanding polymer field due to increased numbers of (co)-monomers authorized by the EU. Key findings and conclusions: Evaluating a polymer regarding the content and migration potential of its oligomers several factors like the separation of oligomers from the material, the choice of suitable separation and detection techniques for identification and quantification and the choice of an appropriate standard have to be considered. Generally, MS technologies coupled to liquid chromatography have been shown to represent the analytical approach of choice. This is, so far as the authors are aware of, the first review exclusively focusing on analytical methods for oligomers as polymer specific substances, which suggests to consider them as a separate polymer related and polymer type specific group besides the so-called non-intentionally added substances (NIAS).
Article
Dependence of the response of a corona-charged aerosol detector (corona CAD) on the concentration and densities of brominated flame retardants and some related substrates was studied. The calibration curves of the substrates did not show linearity and the substrate with a lower density exhibited the stronger response. Regardless of the solvents (chloroform or toluene), and the injected volume of the substrate solution, the signal intensity of the substrate observed by a corona CAD was substantially proportional to 2/3 power law of concentration and proportional to (-2/3) power law of the density of the substrates. These results suggest that the responses should be proportional to the surface area of the particles generated through the drying process in corona CAD. Contrary to the former reports that the detector response of a corona CAD was independent of chemical species, it was proved that the response varies with the density of a substrate.
Article
Cyclic monomer and oligomers are the major migrating substances from polyamide (PA) food contact materials. An increase of caprolactam (+44%) and cyclic oligomer content (+27%, incl. caprolactam) in PA6 was observed by thermal treatment, here by extrusion of a PA6 film from a granulate. Migration experiments with a PA6 and a PA66 packaging film were carried out into food simulants according to directives 85/572/EEC and 82/711/EEC. Contact conditions (2 h/100°C) were chosen for a heat treatment of the food in the packaging, in this case production of scalded sausage. Aqueous and ethanolic food simulants clearly revealed to be the worst case for migration of cyclic PA6 and PA66 monomer and oligomers. Migration of cyclic oligomers into oil was one order of magnitude lower. No migration could be observed into isooctane (<8 µg dm−2). The substitutes for oil, 95% ethanol and isooctane, were inapplicable for simulating migration of cyclic oligomers into oil. Caprolactam showed different migration behaviour compared with cyclic oligomers, migrating into oil and water to the same extent depending on contact conditions. Fifty percent of the extractable caprolactam migrated from a PA6 sausage casing into scalded sausage (4.2 mg kg−1), residual 41% apparently were extracted by the boiling medium or during pretreatment (soaking) of the casing. Potential migration of caprolactam and cyclic oligomers from a PA6 tea bag was found to be 18% of the specific migration limit for caprolactam and 36% of the overall migration limit. Copyright © 2014 John Wiley & Sons, Ltd.
Article
Specific migration levels of monomers and oligomers in polyethylene terephthalate (PET) food containers were determined using HPLC according to the migration testing methods specified by the relevant legislations of the EU and Asian countries (e.g. Korea and Japan). The results of migration from PET bottles and trays using non-fatty simulants under the testing conditions (60 °C/0.5 h) of Asian countries indicated that the values of various monomers and oligomers (TPA, MHET, BHET, A2 group, A3 group, S2 group, S3 group, cyclic dimer, and cyclic trimer) were in between 0.0 and 0.58 μg dm−2. On the other hand, those obtained with the EU conditions (40 °C/10 days) were in the range of 0.0 to 0.94 μg dm−2. The specific migration values of monomers and oligomers into non-fatty simulants tended to be generally higher in testing under the EU conditions than under Asian conditions. Furthermore, when PET samples were tested for migration from fatty foods simulants using n-heptane (at 25 °C/1 h as per Asian conditions) or iso-octane (at 20 °C/48 h as per EU conditions), only cyclic trimer was detected at levels of 0.36 to 1.05 μg dm−2 and 0.05 to 0.55 μg dm−2, respectively. The use of 95% ethanol as an alternative fatty food simulant for the migration tests of PET would be inappropriate, since it might cause overestimated migration compared to the use of other simulants such as n-heptane and iso-octane.
Article
The types and contents of monomers and oligomers in polyethylene terephthalate (PET) food containers were analyzed using HPLC-ESI-MS after being extracted with 50% acetonitrile or dichloromethane using an accelerated solvent extraction unit. The types of cyclic oligomers were classified into first and second series. The first series represented a type of [TG]n composed of terephthalic acid (TPA; T) and monoethylene glycol (EG; G) at a ratio of 1:1. The second series showed a type of [TG]nG in which a single G unit was substituted by diethylene glycol (DEG; GG). The oligomer level extracted using dichloromethane was measured at 4024–11576 mg kg−1. The first series cyclic oligomers, second series cyclic oligomers and linear oligomers constituted 83.0–90.6%, 7.8–14.7% and 1.3–2.8%, of the total extracted oligomers, respectively. The extracted amounts of TPA, monohydroxyethyl terephthalate and bishydroxyethyl terephthalate using 50% acetonitrile were 3.0–28.2 mg kg−1, 16.8–118.2 mg kg−1 and 3.9–26.7 mg kg−1, respectively. The A2, A3, S2 and S3 groups as modified oligomers were detected as 42.9–221.4 mg kg−1, 17.2–250.3 mg kg−1, 1.1–48.1 mg kg−1 and 1.0–19.8 mg kg−1, respectively. The results of this study demonstrate an advanced analytical approach to determine the residual oligomers and monomers in PET products for food use and imply their potential migration to foodstuffs.
In einer Reihe von Polyestern aus Diolen und aromatischen Dicarbonsäuren wurden die cyclischen Oligomeren isoliert und mit Hilfe der Hochdruckflüssigkeitschromatographie quantitativ bestimmt.Der Gehalt an cyclischen Oligomeren hängt von der chemischen Struktur der Polyester und vom Kondensationsverfahren ab. Hauptkomponente ist das cyclische Dimere, bei Poly(ethylenterephthalat), Poly(1,4-dimethylencyclohexanterephthalat) und Poly(1,4-dimethylenbenzolterephthalat) aus Ringspannungsgründen das cyclische Trimere.Bei technischem Poly(1,4-dimethylencyclohexanterephthalat) gelang eine Auftrennung der stereoisomeren cyclischen Oligomeren, die durch die Verwendung eines trans/cis-1,4-Cyclohexandimethanol-Gemisches entstehen.Die cyclischen Oligomeren der Copolyester mit Diolethern enthalten bei niedrigem Modifizierungsgrad nur einen Dioletherrest.Cyclic oligomers have been separated and determined quantitatively by high pressure liquid chromatography on a number of polyesters of the diol-aromatic dicarbonic acid-type.Percentage of cyclic oligomers is related to the chemical structure of the polyesters as well as to the technology of polycondensations. Main component proved to be the cyclic dimer except in case of poly(ethyleneterephthalate), poly(1,4-dimethylenecyclohexaneterephthalate) and poly(1,4-dimethylenebenzeneterephthalate). Here — due to reasons of ring tension — cyclic trimers are predominant.Separation of stereoisomer cyclic oligomers, resulting from use of a trans/cis-1,4-cyclohexanedimethanol blend, could be achieved.Cyclic oligomers of copolyesters with diolethers, if modified to a low degree, only have one diolether group.
Article
Cyclic oligomers are the major substances migrating from polyamide (PA) food contact materials. However, no commercial standards are available for the quantification of these substances. For the first time the quantification of cyclic oligomers was carried out by HPLC coupled with a chemiluminescence nitrogen detector (CLND) and single-substance calibration. Cyclic monomer (MW = 226 Da) and dimer (MW = 452 Da) of PA66 were synthesised and equimolar N detection of CLND to synthesised oligomers, caprolactam, 6-aminohexanoic acid (monomers of PA6) and caffeine (a typical nitrogen calibrant) was proven. Relative response factors (UVD at 210 nm) referring to caprolactam were determined for cyclic PA6 oligomers from dimer to nonamer, using HPLC-CLND in combination with a UVD. A method for quantification of cyclic oligomer content in PA materials was introduced using HPLC-CLND analysis and caffeine as a single nitrogen calibrant. The method was applied to the quantification of cyclic PA oligomers in several PA granulates. For two PA6 granulates from different manufacturers markedly different oligomer contents were analysed (19.5 versus 13.4 g kg⁻¹). The elution pattern of cyclic oligomers offers the possibility of identifying the PA type and differentiating between PA copolymers and blends.
Article
The responses of four different types of aerosol detectors have been evaluated and compared to establish their potential use as a universal detector in conjunction with ultra high pressure liquid chromatography (UHPLC). Two charged-aerosol detectors, namely Corona CAD and Corona Ultra, and also two different types of light-scattering detectors (an evaporative light scattering detector, and a nano-quantity analyte detector [NQAD]) were evaluated. The responses of these detectors were systematically investigated under changing experimental and instrumental parameters, such as the mobile phase flow-rate, analyte concentration, mobile phase composition, nebulizer temperature, evaporator temperature, evaporator gas flow-rate and instrumental signal filtering after detection. It was found that these parameters exerted non-linear effects on the responses of the aerosol detectors and must therefore be considered when designing analytical separation conditions, particularly when gradient elution is performed. Identical reversed-phase gradient separations were compared on all four aerosol detectors and further compared with UV detection at 200 nm. The aerosol detectors were able to detect all 11 analytes in a test set comprising species having a variety of physicochemical properties, whilst UV detection was applicable only to those analytes containing chromophores. The reproducibility of the detector response for 11 analytes over 10 consecutive separations was found to be approximately 5% for the charged-aerosol detectors and approximately 11% for the light-scattering detectors. The tested analytes included semi-volatile species which exhibited a more variable response on the aerosol detectors. Peak efficiencies were generally better on the aerosol detectors in comparison to UV detection and particularly so for the light-scattering detectors which exhibited efficiencies of around 110,000 plates per metre. Limits of detection were calculated using different mobile phase compositions and the NQAD detector was found to be the most sensitive (LOD of 10 ng/mL), followed by the Corona CAD (76 ng/mL), then UV detection at 200 nm (178 ng/mL) using an injection volume of 25 μL.
Article
The universality of the response of the Corona Charged Aerosol Detector (CoronaCAD) has been investigated under flow-injection and gradient HPLC elution conditions. A three-dimensional model was developed which relates the CoronaCAD response to analyte concentration and the mobile phase composition used. The model was developed using the response of four probe analytes which displayed non-volatile behavior in the CoronaCAD and were soluble over a broad range of mobile phase compositions. The analyte concentrations ranged from 1μg/mL to 1mg/mL, and injection volumes corresponded to on-column amounts of 25ng to 25μg. Mobile phases used in the model were composed of 0-80% acetonitrile, mixed with complementary proportions of aqueous formic acid (0.1%, pH 2.6). An analyte set of 23 compounds possessing a wide range of physicochemical properties was selected for the purpose of evaluating the model. The predicted response was compared to the actual analyte response displayed by the detector and the efficacy of the model under flow-injection and gradient HPLC elution conditions was determined. The average error of the four analytes used to develop the model was 9.2% (n=176), while the errors under flow-injection and gradient HPLC elution conditions for the evaluation set of analytes were found to be 12.5% and 12.8%, respectively. Some analytes were excluded from the evaluation set due to considerations of volatility (boiling point <400°C), charge and excessive retention on the column leading to elution outside the eluent range covered by the model. The two-part response model can be used to describe the relationship between response and analyte concentration and also to offer a correction for the non-linear detector response obtained with gradient HPLC for analytes which conform to the model, to provide insight into the factors affecting the CoronaCAD response for different analytes, and also as a means for accurately determining the concentration of unknown compounds when individual standards are not available for calibration.
Article
Recently a new detection method, based upon aerosol charging (the charged aerosol detector (CAD)) has been introduced as an alternative to evaporative light-scattering detector (ELSD), chemiluminescent nitrogen detector and refractive index detector for detection of non-ultraviolet and weakly ultraviolet active compounds and for UV-absorbing compounds in the absence of standards. The content of this review article includes description of operation principle, advantages and disadvantages of CAD system, and short reports of selected applications of this detector. The main advantages of CAD detector are unique performance characteristics: better sensitivity than ELSD system, a dynamic range of up to 4 orders of magnitude, ease of use and constancy of response factors. Both detectors are mass dependent and the response generated does not depend on the spectral or physicochemical properties of the analyte. This attractive feature of a detection technique generating universal response factors is the potential use of a single, universal standard for calibration against which all other compounds or impurities can be qualified. CAD also has the same limitation as ELSD, namely, the response is affected by mobile-phase composition. This problem has been resolved by using inverse gradient compensation as is done for high pressure liquid chromatography and supercritical fluid chromatography. CAD has been applied for the analysis of structurally diverse compounds used in the pharmaceutical, chemical, food, and consumer products industries and in life science research. They include nonvolatile and semivolatile neutral, acidic, basic, and zwitterionic compounds, both polar and nonpolar (e.g. lipids, proteins, steroids, polymers, carbohydrates, peptides).
Article
Ultra-violet spectrophotometry (UV), high performance liquid chromatography (HPLC) and liquid chromatography coupled to mass spectroscopy (LC-MS) were used to identify and quantify oligomers extracted with boiling water from two different nylon 6 films used in boil-in-bag food packaging. The results indicated the loss of up to 1.5% of the original nylon film weight, into the boiling water, as caprolactam and cyclic oligomers up to the nonamer. Extraction time, thickness and type of film used, were found to be parameters which affected the levels of these migrants. These results will be relevant to situations in which food is cooked in the water used to heat the pouch contents.
Article
Metal cans for food use can be coated with lacquers based on polyester resins. Recent research has focussed on the identification and quantification of migrants released by coatings that are potentially absorbable (below 1000 Da). The presented method describes a procedure that was optimized to hydrolyse the polyester migrants into their monomers, polyvalent acids and polyols. The polyols were identified by gas chromatography with flame ionization detection GC-FID and the acids by high-performance liquid chromatography (HPLC) coupled with an ultraviolet and an electrospray ionization-mass selective detector (HPLC-ESI-MSD/UVD), respectively. With the knowledge of the polyester monomers, it was possible--at least tentatively--to identify the main components in the migrate as cyclic oligoesters by HPLC-ESI-MSD/UVD. A cyclic oligomer, CYCLO [3IPA (isophthalic acid) 3EG (ethylene glycol)] was synthesized and characterized by infrared, nuclear magnetic resonance and mass spectrometry as well as by elementary analysis for further confirmation. To determine the amount of migrating cyclic oligoesters, the response of the migrating substances was compared using different detectors, UVD, MSD and evaporative light scattering detector (ELSD). The response of the ELSD was dependent on the molecular weight of the analytes that reduced the accuracy of this detection type. The wavelength with the same absorption coefficient for IPA and terephthalic acid (TPA) was obtained at 232 nm. The UV(232nm) response of an oligoester is proportional to the number of its IPA/TPA moieties, which was verified for several TPA/IPA esters. The amount of the migrating oligoesters was determined using an UV(232nm) calibration of a commercially available TPA ester and the number of IPA/TPA moieties molecules gained from the ESI-MSD spectra. According to this method, the amount of migrating oligoesters below 1000 Da in the 95% ethanol migrate varied from 0.1 to 0.6 mg dm(-2) (0.6-3.6 mg kg(-1) food) in the examined coatings. The determined amounts account for about 50% of the total migrate below 1000 Da.
Article
A new, empirical approach is introduced to correct for the varying response of aerosol-based detectors with the varying composition of the mobile phase during gradient elution in HPLC. A Corona charged aerosol detector was used in the experiments. The detector is characterized by a nearly universal response at a given, constant mobile-phase composition for sufficiently nonvolatile analytes. A second pump was used to deliver an exactly inverse gradient compared to the analytical HPLC system, and both flows were mixed in a tee piece before introduction to the Corona detector. The approach proposed made it possible to extend the universal response from isocratic to gradient elution conditions in HPLC, vastly improving the usefulness of this detection technique. The constant response of the detector obtained in this way was first demonstrated in flow injection analysis. Very similar calibration curves were obtained for six sulfonamide drugs after mobile-phase compensation. The approach was also applied to gradient elution with excellent results. The data were characterized by good precision ranging from 4% RSD at 10 mg/L to 1.6% RSD at 780 mg/L. The average limit of detection with a 2-microL injection was 0.5 mg/L, corresponding to 1 ng injected on the column. The approach proposed allows quantification of unknown compounds, e.g., in pharmaceutical mixtures. Measurement of analytes at a relative concentration of 0.05% versus the main component is demonstrated.
Article
The threshold of toxicological concern (TTC) has been used for the safety assessment of packaging migrants and flavouring agents that occur in food. The approach compares the estimated oral intake with a TTC value derived from chronic oral toxicity data for structurally-related compounds. Application of the TTC approach to cosmetic ingredients and impurities requires consideration of whether route-dependent differences in first-pass metabolism could affect the applicability of TTC values derived from oral data to the topical route. The physicochemical characteristics of the chemical and the pattern of cosmetic use would affect the long-term average internal dose that is compared with the relevant TTC value. Analysis has shown that the oral TTC values are valid for topical exposures and that the relationship between the external topical dose and the internal dose can be taken into account by conservative default adjustment factors. The TTC approach relates to systemic effects, and use of the proposed procedure would not provide an assessment of any local effects at the site of application. Overall the TTC approach provides a useful additional tool for the safety evaluation of cosmetic ingredients and impurities of known chemical structure in the absence of chemical-specific toxicology data.
Scientific Opinion on the safety evaluation of the substance, cyclic oligomers of (butylene terephthalate), CAS No. 263244-54-8, for use in food contact materials: Safety evaluation of the substance cyclic oligomers of (butylene terephthalate), CAS No. 263244-54-8, for use in food contact materials
EFSA Panel on food contact materials, enzymes, flavourings and processing aids (CEF), Scientific Opinion on the safety evaluation of the substance, cyclic oligomers of (butylene terephthalate), CAS No. 263244-54-8, for use in food contact materials: Safety evaluation of the substance cyclic oligomers of (butylene terephthalate), CAS No. 263244-54-8, for use in food contact materials, EFSA Journal. 7 (2009) 1399. doi:10.2903/j.efsa.2009.1399.
Recent developments in the risk assessment of chemicals in food and their potential impact on the safety assessment of substances used in food contact materials
Recent developments in the risk assessment of chemicals in food and their potential impact on the safety assessment of substances used in food contact materials, EFSA J. 14 (2016), http://dx.doi.org/10.2903/j.efsa.2016.4357.
Note for guidance for the preparation of an application for the safety assessment of a substance to be used in plastic food contact materials
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V. Silano, C. Bolognesi, L. Castle, J.-P. Cravedi, K.-H. Engel, P. Fowler, R. Franz, K. Grob, R. Gürtler, T. Husøy, S. Kärenlampi, W. Mennes, M.R. Milana, A. Penninks, M. de F.T. Poç as, A. Smith, C. Tlustos, D. Wölfle, H. Zorn, C.-A. Zugravu, Note for guidance for the preparation of an application for the safety assessment of a substance to be used in plastic food contact materials, EFSA J. 6 (2008), http://dx.doi.org/10.2903/j.efsa.2008.21r.
Identification of oligomers in polyethyleneterephthalate bottles for mineral water and fruit juice
  • A L M Nasser
  • L M X Lopes
  • M N Eberlin
  • M Monteiro
A.L.M. Nasser, L.M.X. Lopes, M.N. Eberlin, M. Monteiro, Identification of oligomers in polyethyleneterephthalate bottles for mineral water and fruit juice, J. Chromatogr. A 1097 (2005) 130-137, http://dx.doi.org/10.1016/j. chroma.2005.08.023.
on plastic materials and articles intended to come into contact with food
Commission Regulation (EU) No 10/2011 of 14 January 2011 on plastic materials and articles intended to come into contact with food, (n.d.) 89.
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  • R S Mccarthy
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