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Detection of aspirin traces in blood by means of surface‐enhanced Raman scattering spectroscopy
Abstract
Aspirin being freely available as an over the counter drug has a high overdose risk and can cause severe health symptoms. The methods used in clinics for the detection of such drugs (pharmaceuticals) in bodily fluids are mostly based on liquid chromatography and mass spectroscopy. These methods are known to be precise; however, they both require long and laborious sample preparation; thus, it takes time to acquire the required information. Because in the case of an overdose, the time has high importance, and faster methods would be beneficial. This work presents an application of a Surface‐enhanced Raman scattering (SERS) spectroscopic method for the detection of salicylic acid as a metabolite of aspirin in the blood serum of the patient under examination. In this research, the various colloidal solutions were employed for the preparation of SERS active substrates. The choice of the most efficient colloidal solution and the challenges of collecting SERS spectra of whole blood or its components are discussed. The spectra of both the model and the real‐life blood samples containing metabolite of aspirin were collected with a Fourier transform Raman spectrometer. The analysis of the collected spectra revealed that label‐free SERS can be used for the detection of salicylic acid with concentration down to 3 mM in blood serum corresponding to consumption of at least eight standard pills of aspirin (equivalent to mild toxicity). The proposed diagnostic method could be applied faster than the standard methods and could allow sensitive and fast diagnosis of aspirin consumption in the human blood. We propose a method for fast and sensitive detection of salicylic acid in blood and blood serum using label‐free Surface‐enhanced Raman scattering spectroscopy by employing colloidal solutions. Samples simulating real‐life conditions (consumption of aspirin dose) were used for testing the sensitivity of the method and its application for point‐of‐care analysis.
... Lastly, the stretching mode of the carbons of the phenyl group was found at 1585 cm −1 . By comparison, only the 809, 1011, 1146 and 1585 cm −1 Raman peaks were observed in the reference samples, while the contribution from dextran after background subtraction was seen only in the carbon/hydrogen bonds [33,34]. Table 1 below summarizes the Raman peaks obtained in the ASA experiments. . ...
... Lastly, the stretching mode of the carbons of the phenyl group was found at 1585 cm −1 . By comparison, only the 809, 1011, 1146 and 1585 cm −1 Raman peaks were observed in the reference samples, while the contribution from dextran after background subtraction was seen only in the carbon/hydrogen bonds [33,34]. Table 1 below summarizes the Raman peaks obtained in the ASA experiments. ...
In this study, we show how surface enhanced Raman spectroscopy (SERS) can be used to monitor the molecular behaviour of aspirin and tenofovir as a means of screening medication for quality control purposes. Gold-coated slides combined with gold/dextran nanoaggregates were used to provide signal enhancement of the drugs using SERS. Aspirin (10% w/v) and tenofovir (20% v/v) were analysed in the presence of the nanomaterials to determine trends in molecular response to changes in gold/dextran concentrations. Qualitative analysis of the functional groups showed specific trends where the peak area increased with polarizability, electron density and decreased atomic radii. Steric hinderance effects also affected the trends in peak area due to the amount of gold/dextran nanoparticles in solution. Statistical analysis provided accurate and precise linear relationships (R2 = 0.99) for the ester and adenine functional groups of aspirin and tenofovir, respectively. From the above findings, the combined use of gold nano-scaffolds and gold/dextran nanomaterials amplified the Raman signal from the drugs to allow for systematic evaluation of their molecular properties. Although more experiments to correlate the findings are still needed, this SERS approach shows great potential as a screening method in the quality control of medications.
... When aspirin is attached to deoxyhemoglobin through the C=O group, the vibrations of C=O in the final molecule (in the attachment region) are suppressed, and the frequency gap continues to have a small intensity in the 1700-1800 cm -1 region as in Fig. 7. The 1700-1800 cm -1 region peaks are found experimentally in aspirin, paracetamol, and ibuprofen [31][32][33]. However, if the attachment is with the OH group, the Raman spectra of the combined molecule will have a nonnegligible intensity of C=O in the 1700-1800 cm -1 region, as in Fig. 8. ...
The interaction of deoxyhemoglobin with antipyretics, including aspirin, paracetamol, and ibuprofen, is investigated using density functional theory with dispersion correction. The formed molecules, after the interaction, are of approximately 1.5-nanometer length, within the nanoscale range. Interaction with water and O2 molecules is included for comparison. Objective: The discussion includes the thermodynamic interaction energies: Gibbs free energy, enthalpy, and entropy, in addition to Raman shifts. The interaction distance and vibrational-induced lines due to interaction are discussed. Results: The two strongest interactions include the interaction of the Fe ion center in deoxyhemoglobin with the carbonyl (C=O) and hydroxy group (OH) in antipyretics. Results show that the interaction distance of the carbonyl group in antipyretics is shorter than the hydroxy group. All interactions of Gibbs energies are less than O2 interaction with ibuprofen, the nearest to O2. Results are in good agreement with experimental results. Conclusions: The importance of this work is that: depending on attachment energy and Raman shifts, the antipyretics can reach different organs with different speeds and different delivered quantities.
... The practical applications of SERS include detection of various trace chemicals, such as pesticides [19,20], drugs [21][22][23] or disease biomarkers in blood [24]. Antibiotics can also be directly detected by SERS, as was summarized in the recent reviews [25,26]. ...
Antibiotics guard us against bacterial infections and are among the most commonly used medicines. The immediate consequence of their large-scale production and prescription is the development of antibiotic resistance. Therefore, rapid detection of antibiotic susceptibility is required for efficient antimicrobial therapy. One of the promising methods for rapid antibiotic susceptibility testing is Raman spectroscopy. Raman spectroscopy combines fast and contactless acquisition of spectra with good selectivity towards bacterial cells. The antibiotic-induced changes in bacterial cell physiology are detected as distinct features in Raman spectra and can be associated with antibiotic susceptibility. Therefore, the Raman-based approach may be beneficial in designing therapy against multidrug-resistant infections. The surface-enhanced Raman spectroscopy (SERS) and resonance Raman spectroscopy (RRS) additionally provide excellent sensitivity. In this review, we present an analysis of the Raman spectroscopy–based optical biosensing approaches aimed at antibiotic susceptibility testing.
... Aspirin is widely used in low doses in preventing antiplatelet aggregations in patients at dicey of occlusive vascular events 9 . Many analytical approaches have been announced for the definition of ASP like spectrophotometry 10 , HPLC 11 , RP-HPLC 12 , UPLC 13 , TLC 14 , capillary zone electrophoresis 15 and raman spectroscopy 16 . SIL is chemically 5-[2-Ethoxy-5-[(4-methylpiperazin-1-yl)sulfonyl]phenyl]-1methyl-3-propyl-1,6-dihydro-7H-pyrazolo [4,3d]pyrimidin-7-one dihydrogen 2hydroxypropane-1,2,3-tricarboxylate, which belongs to phosphodiesterase inhibitors PDEs, specific type 5, Figure 1 8 . ...
... Aspirin is widely used in low doses in preventing antiplatelet aggregations in patients at dicey of occlusive vascular events 9 . Many analytical approaches have been announced for the definition of ASP like spectrophotometry 10 , HPLC 11 , RP-HPLC 12 , UPLC 13 , TLC 14 , capillary zone electrophoresis 15 and raman spectroscopy 16 . SIL is chemically 5-[2-Ethoxy-5-[(4-methylpiperazin-1-yl)sulfonyl]phenyl]-1methyl-3-propyl-1,6-dihydro-7H-pyrazolo [4,3d]pyrimidin-7-one dihydrogen 2hydroxypropane-1,2,3-tricarboxylate, which belongs to phosphodiesterase inhibitors PDEs, specific type 5, Figure 1 8 . ...
... The application of SERS was introduced to detect salicylic acid (a metabolite of aspirin) in patient serum. [120] Under near-infrared (NIR) laser excitation, label-free colloidal SERS J o u r n a l P r e -p r o o f (spherical Ag NPs with citrate-terminated) could be used to detect salicylic acid at a concentration as low as 3 mM in serum, corresponding to the consumption of at least eight standard aspirin pills (mild toxicity). This diagnostic method based on SERS is more rapid than the conventional LC and MS, and can make a sensitive diagnosis of aspirin consumption in blood. ...
Metabolites are important biomarkers in human body fluids, conveying direct information of cellular activities and physical conditions. Metabolite detection has long been a research hotspot in the field of biology and medicine. Surface-enhanced Raman spectroscopy (SERS), based on the molecular “fingerprint” of Raman spectrum and the enormous signal enhancement (down to a single-molecule level) by plasmonic nanomaterials, has proven to be a novel and powerful tool for metabolite detection. SERS provides favorable properties such as ultra-sensitive, label-free, rapid, specific, and non-destructive detection process. In this review, we summarized the progress in recent 10 years on SERS-based sensing of endogenous metabolites at the cellular level, in tissues, and in biofluids, as well as drug metabolites in biofluids. We made detailed discussions on the challenges and optimization methods of SERS technique in metabolite detection. The combination of SERS with modern biomedical technology were also anticipated.
... Limited literature is available concerning the SERS enhancement factor of salicylic acid. To the best of our knowledge, the evaluation of the analytical enhancement factor for salicylic acid adsorbed on silver and gold nanoparticles with 1064 nm excitation is presented only in one of our previous works [59]. The determined enhancement factors for gold and silver nanoparticles prepared with different synthesis methods and stabilizing agents are presented in Table 4. AgNPs-silver nanoparticles. ...
In this research, we have demonstrated that 2D Ti3C2Xn-based MXene (MXene) films are suitable for the design of surface-enhanced Raman spectroscopy (SERS)-based sensors. The enhanced SERS signal was observed for a salicylic acid molecule on Ti3C2Tx-based MXene film. Confirmation of the adsorption of the salicylic acid molecule and the formation of a salicylic acid–MXene complex were determined by experimental SERS-based spectral observations such as greatly enhanced out-of-plane bending modes of salicylic acid at 896 cm−1 and a band doublet at 681 cm−1 and 654 cm−1. Additionally, some other spectral features indicate the adsorption of salicylic acid on the MXene surface, namely, a redshift of vibrational modes and the disappearance of the carboxyl deformation spectral band at 771 cm−1. The determined enhancement factor indicates the value that can be expected for the chemical enhancement mechanism in SERS of 220 for out-of-plane vibrational modes. Theoretical modeling based on density functional theory (DFT) calculations using B3LYP/6311G++ functional were performed to assess the formation of the salicylic acid/MXene complex. Based on the calculations, salicylic acid displays affinity of forming a chemical bond with titanium atom of Ti3C2(OH)2 crystal via oxygen atom in hydroxyl group of salicylic acid. The electron density redistribution of the salicylic acid–MXene complex leads to a charge transfer effect with 2.2 eV (428 nm) and 2.9 eV (564 nm) excitations. The experimentally evaluated enhancement factor can vary from 220 to 60 when different excitation wavelengths are applied.
In this work, a highly selective and sensitive protocol has been developed to detect aspirin (ASP) by using mesoporous silica nanoprobe equipped with molecular imprints and fluorescent carbon dots (ms-MIP-FCDs). The fabrication of nanoprobe is based on the reprocessing of rice straw to fluorescent carbon dots (FCDs) and their amalgamation with molecular imprinting within mesoporous silica network (ms). The molecular imprints for ASP were introduced via sol gel process. The nanoprobe displayed spectrofluorimetric signal due to photoinduced electron transfer between ms-MIP-FCDs and ASP. The synergistic action of mesopores, molecular imprints, and FCDs makes the spectrofluorimetric recognition of ASP quick (in 5 min), sensitive (LOD = 1.16 nM), and selective in the presence of potential competing interferents (such as salicylic acid, methyl salicylate, salsalate, 5-methylsalicyldehyde, naproxen, ketoprofen, diclofenac, mefenamic acid, carbamazepine, and levofloxacin). Furthermore, the method can be successfully applied to detect the ASP from ground water samples with the recoveries in the range of 94.1-104.2% and good precision (relative standard deviation (RSD) < 6.0%). The prepared fluorescent probe also displayed excellent performance with enhanced reusability/durability.
Nanoscale printing is growing rapidly as a feasible fabrication method for a wide range of applications, including electronics and nanooptics, sensors, nanorobots, and energy storage. In today’s cutting-edge technologies, the constantly reducing dimension necessitates the production of complex conductive structures with nanometre resolution., ECAM methods can produce impurity-free metallic conductors with excellent electrical and mechanical properties; however, the true nanoscale resolution remains very challenging. Here, silver nanostructures are synthesized by an ECAM process and investigated as a substrate for surface-enhanced Raman scattering (SERS) detection of aspirin. Various characterizations such as XRD, TEM, HR-TEM, FE-SEM, EDX-mapping, optical, ultraviolet–visible, and Raman spectroscopy are used to analyse ECAM-printed nanostructured silver substrates. A remarkable enhancement factor of ∼ 10⁷ is realized in the silver nanostructured substrates with the detected limit of 10⁻⁸ mol. ECAM printed silver nanostructured substrates can thus be used as viable substrates for SERS applications.
Surface-enhanced Raman Spectroscopy (SERS) is a unique technique that allows us to detect samples in trace quantities. This nanomaterial assisted phenomenon has been extensively studied over past several decades for sensing various chemical, biological and gaseous samples. Present work demonstrates the working of a paper-based SERS substrate to detect and quantify two pharmaceutical drugs- paracetamol, and aspirin in water. The proposed paper-based SERS substrate has been obtained by drop-casting of silver nanoparticles (AgNPs) over a 100 grams per square meter (GSM) paper. The performance of the designed SERS substrate has been initially evaluated with two Raman active samples - malachite green (MG) and rhodamine-6G (R6G). Upon noticing its reliable performance, the usability of the designed SERS substrate has been demonstrated to detect and quantify paracetamol and aspirin in the water medium. The applicability of the proposed SERS substrate in the real field environment has also been demonstrated through detection of these two drug elements in field collected water samples.
Recent advancements in analytical techniques have greatly contributed to the analysis of latent fingermarks’ (LFMs) “touch chemistry” and identification of materials that a suspect might have come into contact with. This type of information about the FM donor is valuable for criminal investigations because it narrows the pool of suspects. It is estimated that at least 30 million people around the world take over-the-counter and prescription nonsteroidal anti-inflammatory drugs (NSAIDs) for pain relief, headaches and arthritis every day. The daily use of such drugs can lead to an increased risk of their abuse. In the present study, Raman spectroscopy combined with multivariate statistical analysis was used for the detection and identification of drug traces in LFMs when NSAID tablets of aspirin, ibuprofen, diclofenac, ketoprofen and naproxen have been touched. Partial least squares discriminant analysis of Raman spectra showed an excellent separation between natural FMs and all NSAID-contaminated FMs. The developed classification model was externally validated using FMs deposited by a new donor and showed 100% accuracy on a FM level. This proof-of-concept study demonstrated the great potential of Raman spectroscopy in the chemical analysis of LFMs and the detection and identification of drug traces in particular.
In this work, surface enhanced Raman scattering (SERS) spectra of aspirin and ibuprofen molecules adsorbed on the surface of silver nets sputtered on porous silicon were collected and analyzed. The bands in the SERS-spectra were correlated in accordance with the type of molecular vibration. Predominantly chemical adsorption of the indicated drugs on the SERS-active substrate through oxygen was observed. It was established that the Raman spectroscopy combined with the SERS-active silver nets makes it possible to detect the aspirin and ibuprofen at 10 ⁻⁶ M concentration.
Surface-enhanced Raman spectroscopy (SERS) is a Raman spectroscopy technique that has been widely used in food safety, environmental monitoring, medical diagnosis and treatment and drug monitoring because of its high selectivity, sensitivity, rapidness, simplicity and specificity in identifying molecular structures. This review introduces the detection mechanism of SERS and summarizes the most recent progress concerning the use of SERS for the detection and characterization of molecules, providing references for the later research of SERS in detection fields.
Because bioequivalence studies are performed using a crossover design, information on the intrasubject coefficient of variation (intra-CV) for pharmacokinetic measures is needed when determining the sample size. However, calculated intra-CVs based on bioequivalence results of identical generic drugs produce different estimates. In this study, we collected bioequivalence results using public resources from the Ministry of Food and Drug Safety (MFDS) and calculated the intra-CVs of various generics. For the generics with multiple bioequivalence results, pooled intra-CVs were calculated. The estimated intra-CVs of 142 bioequivalence studies were 14.7±8.2% for AUC and 21.7±8.8% for CmaxIntra-CVs of Cmaxwere larger than those of area under the concentration-time curve (AUC) in 129 studies (90.8%). For the 26 generics with multiple bioequivalence results, the coefficients of variation of intra-CVs between identical generics (mean±sd (min ~ max)) were 38.0±24.4% (1.9 ~ 105.3%) for AUC and 27.9±18.2% (4.0 ~ 70.1%) for CmaxThese results suggest that substantial variation exists among the bioequivalence results of identical generics. In this study, we presented the intra-CVs of various generics with their pooled intra-CVs. The estimated intra-CVs calculated in this study will provide useful information for planning future bioequivalence studies. (This is republication of the article 'Transl Clin Pharmacol 2017;25:179-182' retracted from critical typographic errors. See the 'Retraction and Republication section of this issue for further information).
In this study surface enhanced Raman scattering (SERS) combined with the isotopic labelling (IL) principle has been used for the quantification of codeine spiked into both water and human plasma. Multivariate statistical approaches were employed for the analysis of these SERS spectral data, particularly partial least squares regression (PLSR) which was used to generate models using the full SERS spectral data for quantification of codeine with, and without, an internal isotopic labelled standard. The PLSR models provided accurate codeine quantification in water and human plasma with high prediction accuracy (Q(2)). In addition, the employment of codeine-d6 as the internal standard further improved the accuracy of the model, by increasing the Q(2) from 0.89 to 0.94 and decreasing the low root-mean-square error of predictions (RMSEP) from 11.36 to 8.44. Using the peak area at 1281 cm(-1) assigned to C-N stretching, C-H wagging and ring breathing, the limit of detection was calculated in both water and human plasma to be 0.7 μM (209.55 ng mL(-1)) and 1.39 μM (416.12 ng mL(-1)), respectively. Due to a lack of definitive codeine vibrational assignments, density functional theory (DFT) calculations have also been used to assign the spectral bands with their corresponding vibrational modes, which were in excellent agreement with our experimental Raman and SERS findings. Thus, we have successfully demonstrated the application of SERS with isotope labelling for the absolute quantification of codeine in human plasma for the first time with a high degree of accuracy and reproducibility. The use of the IL principle which employs an isotopolog (that is to say, a molecule which is only different by the substitution of atoms by isotopes) improves quantification and reproducibility because the competition of the codeine and codeine-d6 for the metal surface used for SERS is equal and this will offset any difference in the number of particles under analysis or any fluctuations in laser fluence. It is our belief that this may open up new exciting opportunities for testing SERS in real-world samples and applications which would be an area of potential future studies.
A rapid and readily reproducible seed-based method for the production of high quality silver nanoprisms in high yield is presented. The edge-length and the position of the main plasmon resonance of the nanoprisms can be readily controlled through adjustment of reaction conditions. From UV-vis spectra of solutions of the nanoprisms, the inhomogeneously broadened line width of the in-plane dipole plasmon resonance is measured and trends in the extent of plasmon damping as a function of plasmon resonance energy and nanoprism size have been elucidated. In addition, an in-depth analysis of the lamellar defect structure of silver nanoprisms is provided that confirms that the defects can lead to a transformation of the crystal structure in the vicinity of the defects. These defects can combine give rise to lamellar regions, thicker than 1 nm, that extend across the crystal, where the silver atoms are arranged in a continuous hexagonal-close-packed (hcp) structure. This hcp structure has a periodicity of 2.50 Å, thus explaining the 2.50 Å lattice fringes that are commonly observed in 〈111〉 oriented flat-lying nanoprisms. A new understanding of the mechanisms behind anisotropic growth in silver nanoprisms is presented.
The ability to control the size, shape, and material of a surface has reinvigorated the field of surface-enhanced Raman spectroscopy (SERS). Because excitation of the localized surface plasmon resonance of a nanostructured surface or nanoparticle lies at the heart of SERS, the ability to reliably control the surface characteristics has taken SERS from an interesting surface phenomenon to a rapidly developing analytical tool. This article first explains many fundamental features of SERS and then describes the use of nanosphere lithography for the fabrication of highly reproducible and robust SERS substrates. In particular, we review metal film over nanosphere surfaces as excellent candidates for several experiments that were once impossible with more primitive SERS substrates (e.g., metal island films). The article also describes progress in applying SERS to the detection of chemical warfare agents and several biological molecules.
Self-medication is defined as the selection and use of medicines by individuals (or a member of the individuals' family) to treat self-recognized or self-diagnosed conditions or symptoms. Several benefits have been linked to appropriate self-medication, among them: increased access to medication and relief for the patient, the active role of the patient in his or her own health care, better use of physicians and pharmacists skills and reduced (or at least optimized) burden of governments due to health expenditure linked to the treatment of minor health conditions However, self-medication is far from being a completely safe practice, in particular in the case of non-responsible self-medication. Potential risks of self-medication practices include: incorrect self-diagnosis, delays in seeking medical advice when needed, infrequent but severe adverse reactions, dangerous drug interactions, incorrect manner of administration, incorrect dosage, incorrect choice of therapy, masking of a severe disease and risk of dependence and abuse. In this short review the author analyzes recent literature on some of the most important dangers related to self-medication practices, particularly: polypharmacy and drug interactions, medications abuse or dependence, misdiagnosis and incorrect choice of treatment. The author also proposes measures that could be adopted in order to solve or improve these issues.
Paracetamol and salicylate are commonly taken in acute overdose. Clinicians have a low threshold for excluding the presence of these two drugs, by ordering laboratory tests in any patient suspected of ingesting an overdose or with an altered mental state.
To test the effectiveness of a new point of care test that qualitatively detects paracetamol and salicylate in blood and to examine the potential time saved by its use.
Prospective multicentre trial.
The new test was compared with laboratory analysis in a routine blood sample taken from patients presenting to emergency departments with suspected overdose.
The test had sensitivities of 98.5% and 88.5%, and specificities of 74.7% and 92%, for paracetamol and salicylate, respectively, at cut-off levels of 25 mg/l and 100 mg/l, respectively The point of care test results were available 2 h before the laboratory result.
This point-of-care test could be used to rule out an overdose with either of these two drugs, and could thus lead to earlier clinical decisions for suspected overdose patients. Recommendations have been made following this trial that the cut-off value for paracetamol should be reduced from 25 mg/l to 12.5 mg/l in order to increase its usefulness. To prevent the test being misread, we also suggest that each device should be embossed to remind users that the presence of a line indicates there is no drug present.
Concentrations of multiple analytes were simultaneously measured in whole blood with clinical accuracy, without sample processing, using near-infrared Raman spectroscopy. Spectra were acquired with an instrument employing nonimaging optics, designed using Monte Carlo simulations of the influence of light-scattering-absorbing blood cells on the excitation and emission of Raman light in turbid medium. Raman spectra were collected from whole blood drawn from 31 individuals. Quantitative predictions of glucose, urea, total protein, albumin, triglycerides, hematocrit, and hemoglobin were made by means of partial least-squares (PLS) analysis with clinically relevant precision (r(2) values >0.93). The similarity of the features of the PLS calibration spectra to those of the respective analyte spectra illustrates that the predictions are based on molecular information carried by the Raman light. This demonstrates the feasibility of using Raman spectroscopy for quantitative measurements of biomolecular contents in highly light-scattering and absorbing media.
Written by a leading expert on Aspirin-related research, this is the most comprehensive treatise on the pharmacological effects and clinical applications of one of the most successful drugs ever. The text is written with a wide audience in mind, and to be readily understandable for clinicians, pharmacists, biomedical researchers and pharmacologists alike. This second, completely revised edition contains the latest results of clinical and pharmacological research on Acetylsalicylic acid, addressing the multiple pharmacological properties of this famous drug with a balanced view on their translation into clinical practice, including prevention from cardiovascular diseases and colorectal cancer.
A liquid chromatography-tandem mass spectrometry method was developed for the simultaneous determination of acetylsalicylic acid (ASP) and its major metabolite, salicylic acid (SAL) in human plasma. The method was validated. ASP and SAL were extracted by single-step liquid-liquid extraction using tert-butyl methyl ether. The ions were detected in multiple reaction monitoring mode at m/z 179.0/137.0 transition for ASP and m/z 136.9/93.0 for SAL. The lower limit of quantification for ASP and SAL was 1 and 80 ng/ml, respectively. The method was successfully applied for the characterization of the plasma concentration levels of ASP and SAL after oral administration of Aspirin Protect 100 to healthy volunteers. The present method can contribute to the improvement of ASP and SAL determination in patients under antithrombotic therapy, and to the reduction of the risk for ASP resistance associated with bioavailability/exposure issues (non-compliance, misdosing, poor absorption).
The Georgia Bureau of Investigation utilized a silylation method of analysis for low molecular weight carboxylic acids in the past. Due to the negative impact such derivatizations can have on gas chromatography-mass spectrometry (GC-MS) systems an alternative means of analysis was investigated. The described method is a whole blood solid phase extraction of valproic acid, salicylic acid and ibuprofen utilizing butylation for sensitivity and improved chromatography by GC-MS. The method produced a limit of detection and limit of quantitation at 1 mg/L for valproic acid, 2 mg/L for salicylic acid and 0.25 mg/L for ibuprofen. The variability based upon the middle of the calibration curve estimated to be 7% for valproic acid, 8% for salicylic acid and 11% for ibuprofen established upon a 95% confidence interval, with the highest percent coefficient of variation being 5.3% for ibuprofen.
The mechanisms of the decarboxylation of salicylic acid anion and its ortho substituted derivatives in gas phase and aqueous solution have been investigated by B3LYP method of DFT theory using the 6-31++G (d,p) basis set. The decarboxylation process includes hydrogen transfers from hydroxyl to carboxyl group and from carboxyl to the α-C of the aryl ring. The mechanism suggested is a pseudo-unimolecular decomposition of the salicylic acid anion and the hydrogen transfer from carboxyl to the α-C of the aryl ring is the rate determining step. Compared with the decarboxylation process in gas phase, the energy barriers in aqueous solution approximately declined by 25%-31%with the water mediation of the hydrogen transfer from carboxyl to the α-C of the aryl ring. The effects of substituents at the ortho position on the decarboxylation process were also investigated. Both the electron donating CH3 and withdrawing group NO2 at the ortho position of carboxyl group can further reduce the reaction energy barriers of the decarboxylation of salicylic acid anions.
Written by a leading expert on Aspirin-related research, this is the first comprehensive treaty of the history, pharmacological effects and clinical applications of one of the most successful drugs ever. The text is written with a wide audience in mind and to be readily understandable for clinicians as well as biomedical researchers and pharmacologists alike. The content is up to date and includes the latest results of clinical and academic research, with a balanced view on the disputed properties of this famous drug.
We report a novel approach for fabricating gold nanostar-functionalized substrates for highly sensitive surface enhanced Raman spectroscopy (SERS)-based chemical sensing. Gold nanostars immobilized on a gold substrate via a Raman silent organic tether serve as the SERS substrate, and facilitate the chemical sensing of analytes that can either be chemisorbed or physisorbed on the nanostars. Our SERS substrates are capable of detecting chemisorbed 4-mercaptobenzoic acid at a concentration as low as 10 fM with a reproducible SERS enhancement factor of 10(9), and enable the semi-quantitative multiplexed identification of analytes from mixtures in which they have been dissolved in variable stoichiometry. Most importantly, they afford the detection of physisorbed analytes, such as crystal violet, with an excellent signal-to-noise ratio, hence serving as a versatile platform for the chemical identification of in principle any molecular analyte. These characteristics make a strong case for the use of our nanostar-based SERS substrate in practical chemical sensing applications.
Raman spectra of aqueous solutions of magnesium acetate at 293 K have been studied in the concentration range 0.65–3.24 M, as have the Raman spectra of the crystallohydrate Mg(CH3COO)2·4H2O. Fourier deconvolution and band fitting techniques have been used to analyse the spectra in three characteristic regions. The gradual evolution of two new components, in addition to the component corresponding to the CC vibration of the free acetate ion, is observed in the CC region of the solutions. These are identified as belonging to mono- and bisacetato complexes. In saturated solutions the bisacetato complexes are the dominating metal-ligand species. Their presence is confirmed also by Fourier deconvolution of the in-plane rocking CO2 vibration.
UV–visible spectra of uric acid as a function of pH have been studied and compared with experimental data. Different quantum methodologies have been employed: CIS–ZINDO, CIS–HF and TD-DFT. Solvent effects were modeled using the COSMO model. To account for the change in maximum absorbance along a variation of pH, different forms of uric acid have been taken into account: uric acid represented the major species at low pH, urate monoanions represented the major components of urate solution at pH 7, and urate dianions represented the major components of urate solution at pH above 10. Our computational results show CIS–ZINDO and CIS–HF quantum methods do not reproduce well experimental absorption spectra whatever the pH. In contrast, TD-DFT in conjunction with the COSMO continuum model gives very good agreement with experimental data and strongly indicates at medium and high pH uric acid solution is composed of a mixing of the different possible existing species. At neutral pH, uric acid exists as a mixture of a major monoanion component and a minor monoanion component, while at high pH, several dianion species seem to coexist.
In this work, surface-enhanced vibrational spectroscopy and normal vibrational spectroscopy as well as density functional theory (DFT) computational methods have been employed to investigate the nature of the chemical adsorption and orientation of the surface species generated from salicylic acid at silver surfaces. The structure of salicylic acid and its IR and Raman spectra are determined at the B3LYP/6-311+G(d,p) level of theory. These results are used in the assignment of the vibrational spectra. Surface-enhanced Raman scattering (SERS) spectra obtained from silver island films thinly coated with salicylic acid confirm chemical adsorption on the Ag nanostructures. To probe the nature of this surface complex, the optimized geometries and IR and Raman spectra of two model salicylate-silver complexes (Ag1 and Ag2) were calculated at the B3LYP/Lanl2DZ level of theory. It was found that good agreement exists between experimentally observed SERS spectra and the simulated SERS spectra of a complex with the salicylate monoanion bound to a Ag+ ion through its carboxylate group (Ag1). The carboxylate silver salt of salicylic acid (essentially the Ag1 complex) was also prepared, and its IR and Raman spectra were recorded for comparison with the surface-enhanced vibrational spectra. These results, along with the application of surface selection rules, suggest that salicylic acid is deprotonated at silver surfaces, interacting through its carboxylate group alone, and is preferentially in a tilted head-on orientation.Key words: chemisorption, salicylic acid, silver, density functional theory, surface-enhanced Raman scattering, reflection-absorption IR spectroscopy, surface-enhanced IR absorption.
The conformation of the 11-membered ring of the lathyrane skeleton has been investigated using NMR spectra and theoretical calculations. Some other skeletons, such as jatrophane, jatrapholane, and tigliane, seem to be derived from this framework, and the conformation is important in connection with the configuration of the resultant diterpenes. The conformation of lathyrane is principally defined by the orientation of the two methyl groups; namely, the methyl groups on C 1 and C 6 directed above or below the ring plane. Theoretical calculations revealed that the predominant conformation is altered depending on the oxygen functional groups on the ring. As far as the bond lengths, bond angles, and dihedral angles are concerned, all calculation methods afforded reasonable results. In contrast, as regards conformational stability, only the ab initio molecular orbital method (RHF/6-31G*) predicted the most stable conformation, consistent with NOE experiments. On the other hand, the stable conformations predicted by the ab initio method (RHF/STO-3G), the semi-empirical molecular orbital method (MOPAC(PM3)), and the molecular mechanics calculations (MM3) did not necessarily agree with the conformers suggested by the NOE experiments.
a b s t r a c t The use of surfactants to affect the shape evolution of silver nanoparticles is explored. This allows one to fine-tune the morphological evolution and the optical properties of the metal nanoparticles. Polyvinyl pyrrolidone (PVP) has been used as a surfactant to control the growth of silver nanoparticles at room tem-perature. In this paper, molecular dynamics simulations were performed to understand regio-selective adsorption of PVP that leads to the preferential growth of silver nanoparticles in dimethylformamide (DMF). The interaction energies between PVP and Ag(1 1 0), Ag(1 0 0) and Ag(1 1 1) crystal planes were cal-culated and in addition the length density profile of the surfactant on silver surfaces was also examined. Importantly, it has been demonstrated that the length distribution profiles analysis obtained from the molecular dynamics study fully explained the adsorption of PVP on the surface of silver nanoparticles through the carbonyl group of the PVP ring. The application of molecular dynamics simulation technique is important in understanding the evolution of silver nanoparticles and is vital in choosing the right surfactants.
The UV-visible spectra of the light emitted during crystallization of Ba(ClO3)2, As2O3, and methyl salicylate are reported and compared to the triboluminescence and photoluminescence spectra. The differences between the crystalloluminescence and triboluminescence spectra of Ba(ClO3)2 show that the former does not arise from fracture of the newly formed crystals. However, in As2O3 and methyl salicylate the spectral similarities suggest similar origins, i.e., crystal fracture. Possible mechanisms and applications are discussed.
Semiempirical, density functional theory (DFT), and ab initio calculations have been performed to assess the relative stabilities of 15 possible tautomer forms of neutral uric acid, and of the different urate mono- and dianion forms. These methods have also been used to compute ionization potentials (IPs) for uric acid and its derived anions. Overall, we have found that semiempirical calculations, in particular PM3, perform well as compared with B3LYP or MP2 computations toward these different structural and chemical properties of uric acid: the triketo form of uric acid is the most stable tautomer form of neutral uric acid. Three other tautomer forms are relatively close in energy, within the range 2–6 kcal/mol above the triketo form, with a mean energy deviation of only 1.3 kcal/mol between PM3 and DFT or ab initio results; the monoanion form of uric acid obtained by abstracting one proton in position 3 (denoted UAN) is the most stable form among all four possible urate monoanions both in gas phase and in solution; the dianion form of uric acid obtained by abstracting two protons, respectively, in positions 3 and 9 of uric acid (denoted UANN) is the most stable urate dianion form both in gas phase and in solution. However, these two most stable species do not have the lowest IPs in solution: among monoanions and dianions, respectively, the species with the lowest IPs are UAN and UANN. © 2006 Wiley Periodicals, Inc. Int J Quantum Chem, 2007
Twelve fasting normal volunteers received three aspirin dosage forms in a single-dose, complete crossover study; the plasma and urine levels of aspirin, salicylic acid, and salicyluric acid were measured for 10 hr. The three dosage forms were an unbuffered tablet, an effervescent solution with 16 mEq of buffer, and an effervescent solution with 34 mEq of buffer. Significant differences in the absorption rate were observed, with the solution having 16 mEq of buffer being fastest, the solution having 34 mEq of buffer being intermediate, and the tablet being slowest. These differences are attributed to gastric emptying rates and tablet dissolution. Urine pH and renal clearance for all three acid compounds are influenced by the buffer during the first 2 hr following dosing but not later. Area under the curve comparisons suggest that ∼20% more aspirin reaches the general circulation intact following the tablet but that the total amount of salicylate absorbed is not different. Further studies are required to select the optimal buffer content to provide rapid absorption with minimal sodium dose and urine alkalinization.
Using light to exchange information offers large bandwidths and high speeds, but the miniaturization of optical components is limited by diffraction. Converting light into electron waves in metals allows one to overcome this problem. However, metals are lossy at optical frequencies and large-area fabrication of nanometer-sized structures by conventional top-down methods can be cost-prohibitive. We show electromagnetic energy transport with gold nanoparticles that were assembled into close-packed linear chains. The small interparticle distances enabled strong electromagnetic coupling causing the formation of low-loss subradiant plasmons, which facilitated energy propagation over many micrometers. Electrodynamic calculations confirmed the dark nature of the propagating mode and showed that disorder in the nanoparticle arrangement enhances energy transport, demonstrating the viability of using bottom-up nanoparticle assemblies for ultracompact opto-electronic devices.
The surface-enhanced raman scattering (SERS) of benzoic acid/benzamide and salicylic acid/salicylamide on silver colloids show important wavenumber shifts with respect to the Raman spectrum of the band assigned to mode 1;ν(ring) when adsorbed on the metal surface (ca. +50 cm(-1)). In the case of the acids, this shift is originated by the deprotonation of the carboxylic group in agreement with the well-known fact that aromatic acids are adsorbed on silver as carboxylates. However, the main conclusion of this work is that a similar behavior is found for the respective amides that do not behave as acids in water solution. The here studied aromatic amides are adsorbed as azanions on silver nanoparticles even at pH 7 and link to the metal through the nitrogen and oxygen atoms of the ionized carboxamide group. This is a very surprising result given that amides are not significantly ionized even at pH 13-14. The deprotonation of these amides is not determined exclusively by the pH, but it is mainly caused by the strong affinity of the anionic species to the metal. Therefore, the SERS must be cautiously used as a universal pH sensor if the adsorption occurs through the ionizable group. In order to support this conclusion, theoretical DFT force field calculations have been carried out, confirming that deprotonated benzamide and salicylamide interact with the metallic surface.
Circulating whole blood levels of aspirin (acetylsalicylic acid) were determined by a method of analysis which instantly stopped enzymatic hydrolysis and yielded a negligible blank reading. It was shown that at 10 min. after ingestion of commercial tablets of buffered or unbuffered aspirin by humans, 50 per cent of the blood salicylic acid was unhydrolyzed aspirin; this decreased to 30 per cent at 20 min.
The biological effects of 1-Sarcosine, 8-Threonine angiotensin II ([Sar1, Thr8]ANG II) on blood pressure, plasma aldosterone concentration (PAC) and plasma renin activity (PRA) were investigated in six normal subjects on an unrestricted diet, and compared with those of 1-Sarcosine, 8-Isoleucine ANG II ([Sar1, Ile8]ANG II) and 1-Sarcosine, 8-Alanine ANG II ([Sar1, Ala8]ANG II). All three ANG II analogues (AIIA) showed agonistic pressor activity, that of [Sar1, Ile8]ANG II being greater than that of [Sar1, Thr8]ANG II or [Sar1, Ala8]ANG II. The antagonistic effect of [Sar1, Thr8]ANG II on blood pressure was less than [Sar1, I1e8]ANG II or [Sar1, Ala8]ANG II. Both [Sar1, Ile8]ANG II and [Sar1, Ala8]ANG II increased PAC and blocked the steroidogenic action of ANG II, while [Sar1, Thr8]ANG II showed little effect on PAC. All three AIIA caused similar suppression of PRA and showed no inhibitory effect on the decrease in PRA produced by ANG II. These results indicate that [Sar1, Thr8]ANG II is an AIIA with weak agonistic pressor action and that it has vascular selective properties. It is also suggested that ANG II receptors in a variety of target organs are heterogeneous.
National synchrotron facilities in Europe need to become more efficient, both technically and administratively, if they are to keep up with the increasing demand from life scientists, according to a report published by the European Science Foundation (ESF) two weeks ago.
The HIV-1 gp120/CD4 interaction shows a large, unprecedented entropy/enthalpy compensation, with the capacity to fine-tune recognition over a broad range of affinity. The intermolecular interaction involves stable hydrophobic contacts with a unique protruding CD4-Phe43 structure surrounded by an intermolecular hydrogen-bond network that covers the hemisphere of the CD4 D1 domain. We have applied a heuristic formula based on the covariance matrix of atom-positional fluctuations to assess the configurational entropy of the gp120/CD4 complex at different levels. The system was dissected into various subsets of atoms to evaluate the entropic contributions of different functional elements. By combining the trajectories of the free and complex forms, further insight into the conformational sampling was extracted. Despite the limited sampling time of 10 ns, the theoretically derived changes in configurational entropy are in fair agreement with the experimentally determined data. The simultaneous evaluation of different interaction modes through a decomposition approach is only feasible with the knowledge of the atomic trajectory of the system. The configurational entropy analysis in terms of combined trajectories presented here shall potentially provide accurate estimations of thermodynamic properties of biomolecules given sufficient sampling of conformational space.
Hydrogen bonding is a fundamental element in protein structure and function. Breaking a single hydrogen bond may impair the stability of a protein. We report an infrared vibrational spectral marker for probing the hydrogen-bond number for buried, protonated Asp or Glu residues in proteins. Ab initio computational studies were performed on hydrogen-bonding interactions of a COOH group with a variety of side-chain model compounds of polar and charged amino acids in vacuum using density function theory. For hydrogen-bonding interactions with polar side-chain groups, our results show a strong correlation between the C=O stretching frequency and the hydrogen bond number of a COOH group: approximately 1759-1776 cm(-1) for zero, approximately 1733-1749 cm(-1) for one, and 1703-1710 cm(-1) for two hydrogen bonds. Experimental evidence for this correlation will be discussed. In addition, we show an approximate linear correlation between the C=O stretching frequency and the hydrogen-bond strength. We propose that a two-dimensional infrared spectroscopy, C=O stretching versus O-H stretching, may be employed to identify the specific type of hydrogen-bonding interaction. This vibrational spectral marker for hydrogen-bonding interaction is expected to enhance the power of time-resolved Fourier transform infrared spectroscopy for structural characterization of functionally important intermediates of proteins.
The surface-enhanced Raman scattering (SERS) of salicylic acid (S) adsorbed on a silver sol in H2O and D2O has been investigated. At pH 5 or greater, the adsorbed species is the salicylate anion (2-hydroxybenzoate anion) (S−), which links to the metal nanoparticle (Agn) through the carboxylate group (S−–Agn). We demonstrate that the selective enhancement of the bands is due mainly to a resonant electron or charge transfer process (ET or CT) from the metallic nanoparticle to the adsorbate, yielding the transient formation of the respective radical dianion (S·2−–Agn+). It is found that the enhanced bands, and especially mode 8a;νring, are related to the differences between the equilibrium structures of the adsorbate in its ground (S−) and CT-excited states (S·2−). © 2006 Wiley Periodicals, Inc. Biopolymers 82: 379–383, 2006
This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com
The growth of gold nanoparticles by reduction by citrate and ascorbic acid has been examined in detail to explore the parameter space of reaction conditions. It is found that gold particles can be produced in a wide range of sizes, from 9 to 120 nm, with defined size distribution, following the earlier work of Turkevich and Frens. The reaction is initiated thermally or in comparison by UV irradiation, which results in similar final products. The kinetics of the extinction spectra show the multiple steps of primary and secondary clustering leading to polycrystallites.
The dependence of the optical properties of spherical gold nanoparticles on particle size and wavelength were analyzed theoretically using multipole scattering theory, where the complex refractive index of gold was corrected for the effect of a reduced mean free path of the conduction electrons in small particles. To compare these theoretical results to experimental data, gold nanoparticles in the size range of 5 to 100 nm were synthesized and characterized with TEM and UV-vis. Excellent agreement was found between theory and experiment. It is shown that the data produced here can be used to determine both size and concentration of gold nanoparticles directly from UV-vis spectra. Equations for this purpose are derived, and the precision of various methods is discussed. The major aim of this work is to provide a simple and fast method to determine size and concentration of nanoparticles.
Our primary goal in this study is to demonstrate that near-infrared Raman spectroscopy is feasible as a rapid and reagentless analytic method for clinical diagnostics. Raman spectra were collected on human sera by use of a 785-nm excitation laser and a single-stage holographic spectrometer. A partial-least-squares method was used to predict the analyte concentrations of interest. The prediction errors of total protein, albumin, triglyceride, and glucose in human sera ranged from 1.0% to 10%, which are highly acceptable for clinical diagnosis, of their mean physiological levels. For investigating the potential application of near-infrared Raman spectroscopy in screening of therapeutical drugs and substances of abuse the concentrations of acetaminophen, ethanol, and codeine in water solution were measured in the same fashion. The errors of the Raman tests for acetaminophen and ethanol are lower than their toxic levels in human serum, and the sensitivity for detection of codeine fails to reach its toxic level.
- Qu J. Y.
The Pharmaceutical Basis of Therapeutics
- A. G. Gilman
- T. W. Rall
- A. S. Nies
- P. Tylor