A P De Leenheer

Ghent University, Gand, Flanders, Belgium

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Publications (257)853 Total impact

  • H. J. Nelis, A. P. De Leenheer
    Journal of Applied Microbiology 03/2008; 70(3):181 - 191. · 2.20 Impact Factor
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    ABSTRACT: An exploratory analysis was performed in order to evaluate the feasibility of building of neural network (NN) systems automating the identification of amphetamines necessary in the investigation of drugs of abuse for epidemiological, clinical and forensic purposes. A first neural network system was built to distinguish between amphetamines and nonamphetamines. A second, more refined system, aimed to the recognition of amphetamines according to their toxicological activity (stimulant amphetamines, hallucinogenic amphetamines, nonamphetamines). Both systems proved that discrimination between amphetamines and nonamphetamines, as well as between stimulants, hallucinogens and nonamphetamines is possible (83.44% and 85.71% correct classification rate, respectively). The spectroscopic interpretation of the 40 most important input variables (GC-FTIR absorption intensities) shows that the modeling power of an input variable seems to be correlated with the stability and not with the intensity of the spectral interaction. Thus, discarding variables only because they correspond to spectral windows with weak absorptions does not seem be not advisable.
    Spectrochimica Acta Part A Molecular and Biomolecular Spectroscopy 09/2006; 64(5):1110-7. · 1.98 Impact Factor
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    ABSTRACT: A rapid and mild procedure for the preparation of [N-7-methyl-11C] caffeine is described. Gaseous 11C-methyl iodide wa led into dimethyl sulphoxide (DMSO), containing theophylline (1,3-dimethylaxanthine) and sodium hydride. Purification of the reaction product was achieved by High Performance Liquid Chromatogrphy (HPLC).
    Journal of Labelled Compounds 07/2006; 19(6):735 - 743.
  • L. M. Thienpont, D. Stöckl, A. P. De Leenheer
    Biological Mass Spectrometry 04/2005; 30(5):772 - 774. · 3.41 Impact Factor
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    ABSTRACT: Mass spectral data are reported for an extended series of synthesized acylcarnitines. Direct mass spectrometry was performed using ionization by fast atom bombardment in combination with high-energy collisional activation and B/E linked scanning. The data show that it is possible to distinguish between isomeric compounds using this technique. Gas chromatographic/mass spectrometric analysis data for acylcarnitines, as their acyloxylactone derivatives, are reported. Both electron impact and chemical ionization modes were used, permitting the unequivocal characterization and identification of the various compounds. In view of the recent marked increase in acylcarnitine profiling activities, the comprehensively reported mass spectrometric and gas chromatographic data may be useful for reference purposes.
    Biological Mass Spectrometry 04/2005; 30(1):69 - 80. · 3.41 Impact Factor
  • André P. de Leenheer, Linda M. Thienpont
    Mass Spectrometry Reviews 02/2005; 11(4):249 - 307. · 7.74 Impact Factor
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    ABSTRACT: To assess the analytical validity of free testosterone (FTe) measurements, a reference measurement procedure (RMP) is required. For steroids, isotope dilution-mass spectrometry is accepted as state-of-the-art technology. Because FTe is defined as the hormone fraction in serum water in equilibrium with the protein-bound fraction, the RMP should include a physical separation step. The use of equilibrium dialysis (ED) or ultrafiltration (UF) is advocated. Our objective was to develop such a candidate RMP. We selected UF combined with isotope dilution-gas chromatography-mass spectrometry (ID-GC/MS) for direct measurement of Te in the ultrafiltrate. After optimization of the UF process, the complete procedure was validated by use of split-sample comparisons with indirect ED (iED) and symmetric dialysis (SyD). The candidate RMP gave maximum within-day, between-day, and total CVs of 3.0%, 3.1%, and 4.3%. The Deming regression equations for the respective method comparisons were: UF-ID-GC/MS = 0.98(iED) - 53 pmol/L (r = 0.94; S(y|x)= 42 pmol/L) and UF-ID-GC/MS = 0.92(SyD) + 21 pmol/L (r = 0.97; S(y|x)= 31 pmol/L). We achieved the objective of a state-of-the-art candidate RMP, which agreed well with iED and SyD. However, we also demonstrated that a degree of discordance remains, which may require a decision from an authoritative organization on the recommended procedure to measure free hormone concentrations.
    Clinical Chemistry 12/2004; 50(11):2101-10. · 7.15 Impact Factor
  • Tom Benijts, Willy Lambert, André De Leenheer
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    ABSTRACT: An analytical method for the determination of 35 endocrine disrupting chemicals (EDCs) present in the aquatic environment was developed and validated. The procedure includes an off-line solid-phase extraction of 500-mL water samples using wide-spectrum polymer packing material combined with two LC-ESI-MS/MS runs, in negative and positive ionization modes. Limits of quantitation were established between 0.1 and 20.0 ng/L. Satisfactory recoveries were obtained ranging from 80.1 to 110.2%. Calibration, using deuterated internal standardization, was performed by linear regression analysis. Linearity (R(2) > 0.99) was demonstrated over individually specified ranges using seven calibration points for each analyte. Intrabatch and interbatch precision, as well as accuracy (n = 5), were investigated at low, medium, and high concentrations. Precision for all compounds, expressed as the RSD, proved to be less than 17.8 and 20.0%, respectively, for intra- and interbatch. Accuracy, expressed as the mean recovery, was between 83.1 and 108.4% at all concentrations. Stability experiments showed no significant loss or deterioration for any of the analytes. Finally, the method was applied on real samples.
    Analytical Chemistry 03/2004; 76(3):704-11. · 5.82 Impact Factor
  • Tom Benijts, Riet Dams, Willy Lambert, André De Leenheer
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    ABSTRACT: In recent years, despite the increasing success of liquid chromatography (LC) coupled to tandem mass spectrometry (MS), reports on matrix susceptibility have shown the limitations of the this powerful analytical technique. Matrix effects (MEs) result from co-eluting residual matrix components affecting the ionization efficiency of target analytes and can lead to erroneous results. The present work evaluates the matrix effect of environmental water samples on 35 endocrine disrupting chemicals (EDCs) in negative and positive LC-ESI-MS/MS. It was shown that mobile-phase additives could significantly influence matrix effects. Addition of acids resulted in a severe signal suppression (average ME%: <65%), and 1 mM ammonium formate increased the average ME% to 84%. The importance of an efficient sample clean-up and internal standardization also was demonstrated. Cleaner extracts resulted in reduced matrix effects (average ME%: 89%) and labeled internal standards proved to have a beneficial effect especially on signal reproducibility (average CV% 4.2% versus 2.6%). The results from the present work indicate that evaluation of matrix effects should become an integrated part of quantitative LC-ESI-MS/MS method development and validation.
    Journal of Chromatography A 03/2004; 1029(1-2):153-9. · 4.61 Impact Factor
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    ABSTRACT: This study evaluates the suitability of gas chromatographic-mass spectrometric (GC-MS) analysis to follow-up the extent of benzodiazepine (mis)use in a Belgian prison population and compares it to other analytical strategies (e.g. screening followed by confirmation of the positive samples). From February to August 1998, 598 persons were jailed of which 188 (31.4% of the incoming detainees) volunteered to be screened. Urine samples (530 in total) were collected on the day of arrival and after 14, 30 and 90 days of imprisonment. All samples were screened by EMIT(R) for benzodiazepines and analysed subsequently by GC-MS. EMIT(R) screening yielded 117 (22.1%) positive samples, a number which increased to 174 (32.8%) after GC-MS analysis. Of these 174 GC-MS positive samples, 119 (68.4%) contained one benzodiazepine while for the remaining samples multiple benzodiazepine (mis)use could be demonstrated. A significant increase in benzodiazepine (mis)use was indicated only from day 0 to day 14 based on the GC-MS results but not on the immunoassay results, even when the latter were complemented with GC-MS analysis of the positively screened samples. The GC-MS data also demonstrated that benzodiazepines are mainly (mis)used by subjects on benzodiazepine prescription as almost 50% of these subjects took additional non-prescribed benzodiazepines. During GC-MS analysis other drugs were co-extracted unintentionally and chromatographed and 23.9% of the volunteers were positive for illegal drugs on the day of arrival. Immunoassay results yield an underestimation of the problem of benzodiazepine (mis)use in prison due to the high false negative rate. GC-MS analysis of all samples therefore is the recommended strategy for this type of longitudinal study as it yields more correct and detailed information than the immunoassay results.
    Addiction 11/2003; 98(10):1427-32. · 4.58 Impact Factor
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    ABSTRACT: This study applied electrospray ionization-isotope dilution-liquid chromatography-tandem mass spectrometry for the evaluation of five urinary C-peptide immunoassays via split-sample measurements. The immunoassays measured in duplicate in the same run, the comparison method in triplicate over different runs. From the data, the within-run imprecision and the method comparison total RSDs were calculated. Regression analysis revealed on the one hand systematic differences, on the other, an excellent correlation between the test and comparison methods. From the spread of the data around the regression line in comparison with the 95% prediction intervals from the total RSD, sample-related effects and/or specificity problems were apparent and investigated.
    Journal of Chromatography B 08/2003; 792(2):249-59. · 2.49 Impact Factor
  • Clinical Chemistry 07/2003; 49(6 Pt 1):992-4. · 7.15 Impact Factor
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    ABSTRACT: We present a fatal case involving the combined ingestion of amphetamine, 3,4-methylenedioxymethylamphetamine, 3,4-methylenedioxyamphetamine, and paramethoxyamphetamine. Various postmortem specimens (e.g., several blood samples, urine, and tissue samples) were analyzed to study the distribution of the compounds and their metabolites in the human body. Quantitation took place using liquid chromatography-sonic spray ionization-mass spectrometry after pretreatment with a liquid-liquid extraction. The medico-legal findings were compatible with a disseminated intravascular coagulation induced by hyperthermia caused by the simultaneous intake of the amphetamine analogues.
    Journal of analytical toxicology 07/2003; 27(5):318-22. · 2.11 Impact Factor
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    ABSTRACT: A quantitative LC-APCI-MS/MS method for simultaneous determination of multiple illicit drugs, methadone, and their metabolites in oral fluid was developed and validated. Sample pretreatment was limited to acetonitrile protein precipitation. LC separation was performed in 25.5 min, with a total analysis time of 35 min. Identification and quantitation were based on selected reaction monitoring. Calibration by linear regression analysis utilized deuterated internal standards and a weighing factor 1/x. Limits of detection and lower limits of quantitation (LOQ) were established between 0.25 and 5 ng/ mL and 0.5-10 ng/mL, respectively. linearity was obtained with an average correlation coefficient (R2) of >0.99, over a dynamic range from the LOQ up to maximum 500 ng/mL The method demonstrated good accuracy, intra- and interbatch precision, recovery, and stability for all compounds. No oral fluid matrix effect was observed throughout the chromatographic run. Protein precipitation provided a fast and simple sample pretreatment, while LC-APCI-MS/MS proved to be a sensitive and rugged quantitative method for multiple illicit and legal drugs in oral fluid. The method proved to be suitable for the evaluation of oral fluid as an alternative matrix to urine for monitoring illicit drug use and for determining oral fluid methadone concentrations in pregnant opiate and/or cocaine addicts.
    Analytical Chemistry 02/2003; 75(4):798-804. · 5.82 Impact Factor
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    ABSTRACT: There is concern about the toxicity of Compound (Co) A. Absorbents differ in the production of Co A during minimal-flow sevoflurane anesthesia. Strong alkali-free Amsorb does not produce Co A. It was our aim to study Superia, another new NaOH- and KOH-free CO(2) absorbent, in minimal-flow anesthesia, compared with KOH-free Sofnolime. After Ethics Committee approval, 14 consenting adult patients were included randomly by using Superia or Sofnolime as the CO(2) absorbent in the compact 750-mL canister of an ADU ventilator. After propofol and remifentanil administration, sevoflurane was given in oxygen and air (500 mL/min; fraction of inspired oxygen, 0.4), aiming at an end-tidal concentration of 2.3%-2.5%; ventilation aimed for 33-35 mm Hg PETCO(2). Compound A inspired (Co A(insp)) and expired (Co A(exp)) samples were taken for analysis, and canister temperatures were measured for 150 min. Statistical analysis was performed with the Friedman test or the Mann-Whitney U-test where appropriate. Correction for multiple testing was used. In the Superia group, no significant amount of Co A was formed, whereas in the Sofnolime group, maximum median (range) inspiratory values of 25 ppm (16 ppm) were found. The intergroup difference was P < 0.05. No difference was noticed between the two groups for the canister CO(2) absorbent temperature. IMPLICATIONS: During minimal-flow 2.3%-2.5% end-tidal sevoflurane, no compound A (Co A) is formed with the NaOH- and KOH-free CO(2) absorbent Superia. Although Co A values with KOH-free Sofnolime are still within reported safe limits, Superia is definitely an alternative for safe clinical practice.
    Anesthesia & Analgesia 01/2003; 95(6):1680-5, table of contents. · 3.30 Impact Factor
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    ABSTRACT: Benzo[a]pyrene diol epoxide (BPDE) was reacted in vitro with (2'-deoxy)nucleotides and with calf thymus DNA. The modified DNA was enzymatically hydrolyzed to the 5'-monophosphate nucleotides using deoxyribonuclease I (DNA-ase I), nuclease P1 and snake venom phosphodiesterase (SVP). Most of the unmodified nucleotides were removed using solid phase extraction (SPE) in a polystyrene divinylbenzene copolymer. Three adducts could be detected and identified using capillary zone electrophoresis(negative)-ion electrospray ionization-mass spectrometry (CZE-(-)-ESI-MS) in conjunction with sample stacking. This way, not only a BPDE-dGMP adduct [(M-H)(-) at m/z 648], a well-known nucleotide adduct, could be retrieved, but also a BPDE-dAMP [(M-H)(-) at m/z 632] and a BPDE-dCMP adduct [(M-H)(-) at m/z 608] could be detected for the first time. The presence of the prominent ion at m/z 195 (the deoxyribose-phosphate ion) in the three low-energy collision-activated decomposition (CAD) spectra indicated that the adducts were formed through base-alkylation. CZE-positive ion ESI-MS/MS experiments were performed to obtain further information on base-alkylation. The absence of the loss of NH(3) from the nucleobase in each CAD spectrum points to an alkylated exocyclic NH(2) position of the nucleobase. So, the three adducts could be identified as BPDE-N(2)-dGMP, BPDE-N(6)-dAMP and BPDE-N(4)-dCMP using CZE-ESI-MS and CZE-ESI-MS/MS.
    Electrophoresis 01/2003; 23(24):4092-103. · 3.26 Impact Factor
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    ABSTRACT: A few days after her admittance to a hospital for a suicide attempt with benzodiazepines, a 15-year-old girl was found dead in bed. At autopsy, no specific anatomo-pathologic cause of death was identified. Systematic toxicological analysis (HPLC-DAD, GC-NPD, and GC-MS) of postmortem blood and urine revealed the presence of high concentrations of flecainide and its two major metabolites. Flecainide is a class IC anti-arrhythmic drug causing a decreased intracardiac conduction velocity in all parts of the heart. To identify and quantitate flecainide together with its metabolites in blood, urine, and other toxicologically relevant matrices, a new method was developed using high-performance liquid chromatography with diode-array detection. All compounds were separated on a Hypersil BDS phenyl column using water, methanol, and 1.5M ammonium acetate in a gradient system. Chromatographic analysis was preceded by an optimized solid-phase extraction procedure on RP-C18 extraction columns. The flecainide concentrations in blood and urine were 18.73 and 28.3 mg/L, respectively, and the metabolites were detected only in urine at the following concentrations: 9.4 mg/L for meta-O-dealkylated flecainide and 8.59 mg/L for meta-O-dealkylated flecainide lactam. Based on these results, it was concluded that the suicide was consistent with an overdose of this anti-arrhythmic drug.
    Journal of analytical toxicology 01/2003; 27(1):47-52. · 2.11 Impact Factor
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    ABSTRACT: A sonic spray ionization liquid chromatography/mass spectrometry (LC/SSI-MS) procedure combined with off-line solid-phase extraction was optimized for the analysis of 20 endocrine-disrupting chemicals (EDCs) in water samples. Method development included a comparison of the novel sonic spray ionization (SSI) with more traditional ion sources, i.e. pneumatically assisted electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI). It was demonstrated that SSI and ESI spectra were very similar, but were more prone to the formation of solvent cluster ions as compared with APCI spectra. This phenomenon was most prominent for SSI and resulted in an increased chemical background in full-scan mass spectra. However, this chemical noise did not affect the overall sensitivity of SSI and ESI. After optimization of LC and MS parameters, the LC/SSI-MS method was validated. Recoveries ranged from 76.3 up to 113.4% for all compounds. Limits of detection (LOD) and quantitation (LOQ) were established between 3.0 and 11.5 ng/L and 9.9 and 38.0 ng/L, respectively. Within-day (n = 5) and between-day (n = 5) reproducibility were investigated at three levels and ranged from 3.3-16.5% and 7.6-19.2%, respectively. Eight-point calibration curves were established and showed linearity for all compounds (r(2) > 0.987) over a linear dynamic range of 10-10 000 ng/L.
    Rapid Communications in Mass Spectrometry 01/2003; 17(16):1866-72. · 2.51 Impact Factor
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    ABSTRACT: The effects of vitamin C (ascorbic acid, AA) and vitamin E (tocopherol) on the maternal performance and offspring quality of the freshwater prawn Macrobrachium rosenbergii were investigated. Prawn females were fed four diets containing different levels of 2-ascorbyl-l-polyphosphate (ApP) and α-tocopherol acetate (α-TA) during 155 days. Three diets contained increasing AA levels (59, 121 and 918 μg g−1 DW) and a basal level of α-TA (around 300 μg g−1 DW), while a fourth diet contained comparatively higher α-TA levels (899 μg g−1 DW) combined with 957 μg AA g−1 DW. Higher dietary levels of AA and α-TA did not affect moulting, growth, or mortality rates of the broodstock. Also, breeding frequency and fecundity were not related to the dietary treatments. However, the contents of AA and α-tocopherol in the midgut gland, ovary, eggs, and newly hatched larvae increased along with higher dietary levels of these vitamins. Larvae from females fed higher levels of AA and α-TA tended to present an increased tolerance when exposed to increasing ammonia concentrations. The present results therefore suggest that broodstock diets containing around 60 μg AA g−1 DW and 300 μg α-TA g−1 DW are sufficient to ensure proper reproduction and offspring viability. However, feeding M. rosenbergii females higher dietary levels of both AA and α-TA (each around 900 μg g−1 DW) might increase larval quality, as demonstrated in this study by the higher tolerance to the exposure to ammonia.
    Aquaculture. 01/2003;
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    ABSTRACT: A method using liquid chromatography coupled to tandem mass spectrometry is described for the determination of drugs of abuse in oral fluid. The method is able to simultaneously quantify amphetamines (amphetamine, methamphetamine, MDA, MDMA and MDEA), opiates (morphine and codeine), cocaine and benzoylecgonine. Only 200 micro of oral fluid is spent for analysis. The sample preparation is easy and consists of mixed mode phase solid-phase extraction. Reversed-phase chromatography is carried out on a narrow bore phenyl type column at a flow-rate of 0.2 ml/min. A gradient is applied ranging from 6 to 67.6% methanol with ammonium formate (10 mM, pH 5.0) added to the mobile phase. The column effluent was directed into a quadrupole-time-of-flight instrument by electrospray ionization, without the use of a splitter. A validation study was carried out. Recovery ranged from 52.3 to 98.8%, within-day and between-day precision expressed by relative standard deviation were less than 11.9 and 16.8%, respectively, and inaccuracy did not exceed 11.6%. The limit of quantification was 2 ng/ml (0.66 x 10(-5)-1.48 x 10(-5) M) for all compounds. Internal standards were used to generate quadratic calibration curves (r(2)>0.999). The method was applied to real samples obtained from suspected drug users. An interference was observed from the device used to sample the oral fluid, consequently this was excluded from the method which was validated on oral fluid obtained by spitting in a test-tube.
    Journal of Chromatography B 11/2002; 779(2):321-30. · 2.49 Impact Factor

Publication Stats

2k Citations
853.00 Total Impact Points

Institutions

  • 1982–2006
    • Ghent University
      • • Faculty of Pharmaceutical Sciences
      • • Laboratory of Microbiology
      Gand, Flanders, Belgium
  • 1980–1990
    • Universitair Ziekenhuis Ghent
      Gand, Flanders, Belgium