Trimethylsilyldiazomethane (TMSD) as a new derivatization reagent for trace analysis of selected non-steroidal anti-inflammatory drugs (NSAIDs) by gas chromatography methods

Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most common groups of pharmaceuticals detected in environmental matrices. Although several derivatization procedures have been employed in the gas chromatographic analysis of NSAIDs, the application of trimethylsilyldiazomethane has never yet been reported. This work has studied the derivatization of widely used NSAIDs (ibuprofen, ketoprofen and naproxen) by trimethylsilyldiazomethane. Special emphasis was placed on the influence of temperature and reaction time on the reaction yield, and on the determination of the instrumental detection limit. The results are compared with those obtained by methylation using boron trifluoride methanol solution, and by silylation with a mixture of N,O-bis(trimethylsilyl)trifluoroacetamide and trimethylchlorosilane (99:1, v/v) and with N-methyl-N-[tert-butyldimethylsilyl]trifluoroacetamide. The derivatization of ibuprofen, ketoprofen and naproxen by trimethylsilyldiazomethane was shown to be simple, fast, efficient, and suitable for trace analysis (the respective instrumental detection limits for ibuprofen naproxen, and ketoprofen were 2, 4, and 4 ng). Trimethylsilyldiazomethane can be used as an alternative reagent for determining acidic drugs in environmental matrices.     

Occurrence,fate and removal efficiencies of pharmaceuticals in wastewater treatment plants (WWTPs) discharging in the coastal environment of Algiers

In the last few decades, the presence of pharmaceutical products in the environment is known under the name of emerging contaminants. These substances can enter the aquatic environment via different sources, as parent compounds, metabolites or a combination of both. In this work, we have investigated the presence of four pharmaceutical active compounds belonging to the group of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), in wastewater, surface water and drinking water of Algiers, which have a direct impact on the Mediterranean Sea. The target analytes (ibuprofen (IBU), naproxen (NAP), ketoprofen (KET), and diclofenac (DIC)), were extracted from the water samples by using Solid Phase Extraction Oasis^® HLB Cartridges; the identification and quantification were realized by Gas Chromatography–Mass Spectrometry (GC–MS). To obtain the best resolution and precision, N-methyl-N-(trimethylsilyl) trifluoroacetamide (MSTFA) was used as the derivatization reagent and ibuprofen-d₃ was used as the internal standard. The obtained recoveries were good, ranging from 82% for ketoprofen to 120% for naproxen with relatively small standard deviations (≤20%). The target compounds were detected in wastewater, influent/effluent with concentrations ranging from 155.5 to 6554 ng/L, implicating removal efficiencies of wastewater treatment plants (WWTPs), between 30.3 and 95%. The surface water was also contaminated with pharmaceuticals from 72.9 ng/L for diclofenac to 228.3 ng/L for naproxen. In addition, the occurrence of ibuprofen and ketoprofen in drinking water, at concentrations of 142.1 and 110.9 ng/L, respectively, attracts concerns about possible impacts on human health.     

Determination of acidic drugs in sewage water by gas chromatography-mass spectrometry as tert.-butyldimethylsilyl derivatives

A procedure is described for the determination of five acidic non-steroidal anti-inflammatory pharmaceuticals (ibuprofen, naproxen, ketoprofen, tolfenamic acid and diclofenac) in sewage water. The analytical method involves the concentration of water samples using a solid-phase extraction polymeric sorbent, functionalized with N-vinylpyrrolidone. Analytes were eluted with ethyl acetate. derivatized using N-methyl-N-(tert.-butyldimethylsilyl)trifluoroacetamide (MTBSTFA) and analyzed by GC-MS. Influence of time, temperature and volume of MTBSTFA in the yield of the derivatization step were studied in detail using a factorial central composite design. Quantification limits of the analytical procedure for 500 ml of sewage water ranged from 20 to 50 ng/l. Recoveries from 90 to 115% were found for sewage water samples spiked with the studied compounds at the low ng/ml level. Results obtained for real samples show the presence of ibuprofen and naproxen in both influent and effluent of a sewage water treatment plant.     

A new sample preparation method for determination of acidic drugs in sewage sludge applying microwave assisted solvent extraction followed by gas chromatography-mass spectrometry

This paper presents a new sample preparation procedure for determination of selected acidic pharmaceuticals (ibuprofen, naproxen, ketoprofen, and diclofenac) in sewage sludge using microwave assisted solvent extraction, dispersive matrix extraction (DME) followed by the conventionally applied solid phase extraction (SPE), derivatization, and gas chromatography-mass spectrometry. The recoveries calculated from analytical data of spiked sludge samples changed in the range of 80-105% ± 15% for the four pharmaceuticals in mixed and activated sludge depending on the efficiency of the clean-up procedure. The measured concentration values of ibuprofen and naproxen were identical in the mixed and the activated sludge samples. However, ketoprofen and diclofenac showed about twice as high concentration in activated sludge than in the mixed one independently of the applied extraction method. The typical concentration ranges of ibuprofen, naproxen, ketoprofen and diclofenac in sewage sludge were 10-30 ng/g, 30-50 ng/g, 50-130 ng/g, and 50-140 ng/g respectively.     

Enantioselective analysis of ibuprofen, ketoprofen and naproxen in wastewater and environmental water samples

A highly sensitive and reliable method for the enantioselective analysis of ibuprofen, ketoprofen and naproxen in wastewater and environmental water samples has been developed. These three pharmaceuticals are chiral molecules and the variable presence of their individual (R)- and (S)-enantiomers is of increasing interest for environmental analysis. An indirect method for enantioseparation was achieved by the derivatization of the (R)- and (S)-enantiomers to amide diastereomers using (R)-1-phenylethylamine ((R)-1-PEA). After initial solid phase extraction from aqueous samples, derivatization was undertaken at room temperature in less than 5 min. Optimum recovery and clean-up of the amide diastereomers from the derivatization solution was achieved by a second solid phase extraction step. Separation and detection of the individual diastereomers was undertaken by gas chromatography-tandem mass spectrometry (GC-MS/MS). Excellent analyte separation and peak shapes were achieved for the derivatized (R)- and (S)-enantiomers for all three pharmaceuticals with peak resolution, R(s) is in the range of 2.87-4.02 for all diastereomer pairs. Furthermore, the calibration curves developed for the (S)-enantiomers revealed excellent linearity (r(2) ≥ 0.99) for all three compounds. Method detection limits were shown to be within the range of 0.2-3.3 ng L(-1) for individual enantiomers in ultrapure water, drinking water, surface water and a synthetic wastewater. Finally, the method was shown to perform well on a real tertiary treated wastewater sample, revealing measurable concentrations of both (R)- and (S)-enantiomers of ibuprofen, naproxen and ketoprofen. Isotope dilution using racemic D(3)-ibuprofen, racemic D(3)-ketoprofen and racemic D(3)-naproxen was shown to be an essential aspect of this method for accurate quantification and enantiomeric fraction (EF) determination. This approach produced excellent reproducibility for EF determination of triplicate tertiary treated wastewater samples.     

In situ aqueous derivatization and determination of non-steroidal anti-inflammatory drugs by salting-out-assisted liquid-liquid extraction and gas chromatography-mass spectrometry

A new analytical method for the determination of trace levels of five non-steroidal anti-inflammatory drugs (NSAIDs: clofibric acid, ibuprofen, naproxen, diclofenac and ketoprofen) in water samples is described. The analytical procedure involves in situ aqueous derivatization with N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDC) and 2,2,2-trifluoroethylamine hydrochloride (TFEA) and salting-out liquid-liquid extraction (SALLE), followed by gas chromatography-programmed temperature vaporizer-mass spectrometry (GC-PTV-MS). The influence of several parameters on the efficiency of the derivatization (stirring time, reaction time, reagent concentration and pH), and the extraction (solvent, volume, salts and stirring time) and injection steps (liner, injection volume, liner temperature, injection time, venting time and venting flow) was investigated. The detection limits of the method in water varied from 0.042 μg/L for ibuprofen to 1.2 μg/L for ketoprofen. The relative standard deviations (RSD) values were found to be relatively low (<10% for all compounds). The methodology developed was applied to the determination of NSAIDs in several environmental matrices including tap, river, sea and influent and effluent waste water samples. The results obtained show the presence of ibuprofen and naproxen in the influent waste water sample.     

Microextraction by packed sorbent for the analysis of pharmaceutical residues in environmental water samples by in situ derivatization-programmed temperature vaporizer-gas chromatography-mass spectrometry

The present work describes the development and validation of a method for the determination of five non-steroidal anti-inflammatory drugs (NSAIDs: clofibric acid, ibuprofen, naproxen, diclofenac and ketoprofen) in water samples. The fully automated method includes in situ aqueous derivatization followed by analyte enrichment by microextraction by packed sorbent (MEPS) coupled directly to programmed temperature vaporizer-gas chromatography-mass spectrometry (PTV-GC-MS). The MEPS variables, such as sample volume, elution solvent, elution volume, fill and injection speed and washing steps were optimized. It was possible to use the MEPS polymer (silica-C18) 250 times. Ibuprofen-d3 was used as internal standard. The reproducibility of the method, calculated as the relative standard deviation (RSD), was below 10% for all compounds. Detection limits in ultrapure water were between 3.0 and 110 ngL(-1) for ibuprofen and ketoprofen, respectively. External calibration was used in the determination of NSAIDs in several types of water samples, including tap, river, sea and influent and effluent wastewater. The results obtained revealed the presence of ibuprofen and naproxen in the influent wastewater sample and of naproxen in the effluent wastewater sample.     

The role of the acquisition methods in the analysis of the non-steroidal anti-inflammatory drugs in Danube River by gas chromatography - mass spectrometry

In this paper authors describe a GC-MS acquisition study, relating to the most common, non-steroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen, naproxen, ketoprofen and diclofenac. As novelties to the field, for the trimethylsilyl (TMS) oxime ester derivatives of NSAIDs, at first, a tandem mass spectrometric (MS/MS) acquisition method has been developed, and, also for the first time, the three acquisition techniques, the full scan (FS), the selective ion monitoring (SIM) and the currently optimized MS/MS ones, have been compared: all three in parallel, under strictly the same derivatization/instrumental conditions, both from model solutions and from the Danube River samples. Critical evaluation of the three acquisition protocols was collated on their analytical performances and validated with the same characteristics like the six point calibration curve, the relative standard deviation percentages (RSD%) of parallel tests, the limit of quantitation (LOQ) and the instrumental limit of quantitation (ILQ) values. Data of six point calibration (r² ≥ 0.997) and RSD% (average: 5.8 RSD%) values proved to be independent on the acquisition methods, while, LOQ and ILQ values furnished considerable differences. Decreasing LOQ data, (expressed in ng/L concentrations) were obtained in the FS, SIM, MS/MS line for ibuprofen (1.0, 0.43, 0.41), naproxen (1.1, 1.0, 0.42), ketoprofen (2.6, 1.0, 0.49) and diclofenac (1.4, 0.41, 0.21), respectively. The same trend was determined in terms of the ILQ values. The practical utility of the optimized MS/MS technique was confirmed by the quantitation of the NSAID contents of the Danube River samples, determined by all three acquisition techniques. Results obtained confirmed the primary importance of the MS/MS acquisition method, even in comparison to the SIM one: avoiding the extreme overestimation of the ibuprofen (≈100%) and ketoprofen (≈400%) concentrations in the Danube River samples.     

Removal of pharmaceutical residues in a pilot wastewater treatment plant

Concern is growing over the contamination of the environment with pharmaceutical residues, among which non-steroidal anti-inflammatory drugs (NSAIDs) are one of the most abundant groups. Their widespread appearance in the aquatic environment is because of their high consumption and their incomplete removal during wastewater treatment. Because effective operation of wastewater-treatment plants is important for minimising the release of xenobiotic compounds, for example pharmaceutical products, into the aquatic environment, our study focuses on removal of commonly used NSAIDs (ibuprofen, naproxen, ketoprofen, diclofenac) and clofibric acid in a specially designed small-scale pilot wastewater treatment plant (PWWTP). This study shows that, except for diclofenac, steady-rate removal of NSAIDs over a two-year monitoring period has been achieved. Elimination of the compounds in the PWWTP was ≥87% for ibuprofen, naproxen and ketoprofen but only 49–59% for diclofenac. We also studied clofibric acid. Results after one month of operation revealed 30% elimination with no sign of adaptation by the biomass. Also described are degradation products of diclofenac, which we were able to identify because of the similarity of their mass spectra with those in the NIST library and by comparing the retention times of different compounds. Although the structures of these compounds were confirmed with a high probability (99%), we still need to compare the fragmentation of authentic compounds with degradation products formed under our experimental conditions. Degradation products of ibuprofen, naproxen, ketoprofen, and clofibric acid were found but these must be identified by use of high-resolution mass spectrometry and analysis of authentic compounds.     

Optimizing gas chromatographic-mass spectrometric analysis of selected pharmaceuticals and endocrine-disrupting substances in water using factorial experimental design

An analytical method based on gas chromatography-mass spectrometry (GC-MS) has been developed to simultaneously determine selected acidic and neutral pharmaceuticals and endocrine-disrupting substances in surface and tap water. Solid-phase extraction (SPE) with Oasis HLB cartridges is followed by derivatization of the target analytes in the eluted extract. Derivatization was systematically optimized by employing a factorial experimental design. More specifically a central composite design was applied to search for the optimal conditions of the derivatization process and it was demonstrated that N-methyl-N-tert-butyl-dimethysilyl-trifluoroacetamide (MTBSTFA) had a better overall performance compared to N,O-bis(trimethylsilyl) trifluoroacetamide (BSTFA). The influence of solvent ratios and elution volumes while using SPE were also studied using a factorial design. The method was developed successfully for most of the selected compounds [i.e. ibuprofen, salicylic acid, gemfibrozil, naproxen, triclosan, propranolol, diclofenac, carbamazepine, 4-octylphenol (OP), 4-nonylphenol (NP), nonylphenol-monoethoxylate (NP1EO), nonylphenoxyacetic acid (NP1EC), estrone (E1), and 17alpha-ethinyloestradiol (EE2)]. Relative recoveries for spiked river and tap water ranged from 47 to 130% and 60-109%, respectively. Typical limits of detection were less than 5 ng/L in tap water and less than 10 ng/L in river water. Twelve target compounds were detected in river and tap water samples using the developed method. This method is currently used in bench-scale drinking water treatment studies.     

An analytical method for the simultaneous trace determination of acidic pharmaceuticals and phenolic endocrine disrupting chemicals in wastewater and sewage sludge by gas chromatography-mass spectrometry

This article presents an analytical method based on solid-phase extraction (SPE) and gas chromatography coupled with mass spectrometry for the simultaneous determination of the most frequently used acidic pharmaceutical residues, ibuprofen, diclofenac, naproxen and ketoprofen (KFN), and phenolic endocrine disruptors, bisphenol (BPA), triclosan (TCS), nonylphenol, nonylphenol monoethoxylate and nonylphenol diethoxylate, in wastewater and sewage sludge samples. In the first phase of the study, each compound has been characterized individually and afterwards in mixture as a trimethylsilyl derivative in order to identify the characteristic ions (m/z ratio) constituting the mass spectrum and to choose the ions for quantification and confirmation. Subsequently, derivatization was evaluated by testing different variables such as the volume of the derivatization solvent bis(trimethylsilyl)trifluoroacetamide and the effect of each catalyst, pyridine and 1% trimethyl chlorosilane, in the derivatized solution. For the analysis of wastewater samples, two commercial SPE cartridges, C18 and Oasis HLB, were compared for their extraction efficiency of the target compounds. The key parameter of extraction procedure included the effect of pH (2.5, 5.3 and 7) of the loading solution. For solid samples, parameters such as the extracted biomass, the volume of the extraction organic solvent and the effect of matrix interferences in chromatographic analysis were evaluated. By using C18 cartridges as purification procedure and ultrasound sonication, satisfactory mean relative recoveries with BPA-d16 and meclofenamic acid as surrogates were obtained ranging from 91% to 117% for wastewater and 84% to 107% for sewage sludge samples. Nine-point calibration of the standard mixture was performed by linear regression analysis with a correlation coefficient >0.99 for all the tested compounds. Limits of detection for the developed methods were established between 0.3 (KFN) and 14.8 (BPA) ng L⁻¹, and 15.0 (TCS) and 32.9 (BPA) ng g⁻¹ for wastewater and sewage sludge, respectively. Application to real samples of the wastewater treatment plant in Athens, the capital of Greece, demonstrated the presence of all tested compounds in most of the samples.     

Investigation of acidic pharmaceuticals in river water and sediment by microwave-assisted extraction and gas chromatography–mass spectrometry

Investigations were performed along the Danube river at Budapest (Hungary) by collecting water and sediment samples simultaneously for 1 year in order to clarify the possible hazard of selected acidic pharmaceuticals (ibuprofen, naproxen, ketoprofen, and diclofenac) on the water supply used for the production of drinking water by bank filtration. In the case of water samples, the sample preparation procedure included solid phase extraction (SPE), meanwhile, in the case of sediment samples, microwave-assisted extraction (MAE) followed by dispersive matrix extraction (DME) for pre-cleaning as well as SPE for enrichment. The quantification was carried out using gas chromatography–mass spectrometry (GC–MS). The calculated recoveries were 97–99% (± 7%) for the water and 95–103% (± 12%) for the sediment samples. In the river water, ketoprofen concentration was always below the limit of quantification (LOQ) level; ibuprofen, naproxen and diclofenac could be quantified in the range of 8–50, 2–30, 7–90 ng/L. In sediments, only naproxen and diclofenac were found in the range of 2–20 and 5–38 ng/g, respectively. According to the obtained results, the concentration ratios of the two phases linearly depended on the total organic carbon content (TOC) of the sediments at each sampling date. The linear regressions were 0.925 and 0.946 for naproxen and diclofenac, respectively.     

Rapid qualitative analysis of 2 flavonoids,rutin and silybin,in medical pills by direct analysis in real‐time mass spectrometry (DART‐MS) combined with in situ derivatization

Direct analysis in real‐time mass spectrometry (DART‐MS) with in situ silylation was used for the rapid analysis of the flavonoids silybin ((2R,3R)‐3,5,7‐trihydroxy‐2‐[3‐(4‐hydroxy‐3‐methoxyphenyl)‐2‐hydroxymethyl‐2,3‐dihydrobenzo[1,4]dioxin‐6‐yl]chroman‐4‐one) and rutin (quercetin‐3‐O‐rutinoside). Three different derivatization reagents, hexamethyldisilazane/trimethylchlorosilane/pyridine (HMDS/TMCS/pyridine), N,O‐bis(trimethylsilyl)acetamide/trimethylchlorosilane/N‐trimethylsilyimidazole (BSA/TMCS/TMSI), and N,O‐bis(trimethylsilyl)trifluoroacetamide/trimethylchlorosilane (BSTFA/TMCS), were applied. Silybin and rutin were detected with various degrees of silylation, and the formation of dimers with pyridine and imidazole was also observed. HMDS/TMCS/pyridine was the best choice for the DART‐MS analysis of silybin, and BSA/TMCS/TMSI was the most effective for the detection of rutin. The effects of the DART source temperature on desorption, ionization, in‐source fragmentation, dimer formation, and hydrolysis of the trimethylsilyl groups were also studied. In addition, the collision‐induced dissociation properties of the derivatized silybin and rutin were explored. With our in situ silylation method, the derivatized bioactive compounds in intact medical pills could also be detected by DART‐MS.     

Determination of acidic pharmaceutical products and carbamazepine in roughly primary-treated wastewater by solid-phase extraction and gas chromatography–tandem mass spectrometry

A gas chromatography–tandem mass spectrometry (GC–MS/MS) method has been developed for the determination of selected pharmaceutical residues (carbamazepine, salicylic acid, clofibric acid, ibuprofen, 2-hydroxy-ibuprofen, fenoprofen, naproxen, ketoprofen, diclofenac, and triclosan) in sewage influent and roughly primary-treated effluent. The method involved solid-phase extraction (SPE) with polymeric sorbents, and two SPE cartridges were compared for the extraction and elution of the targeted compounds in complex matrices. A successful chemical derivatization of carbamazepine and acidic compounds using N,O-bis(trimethylsilyl) trifluoroacetamide +10% trimethylchlorosilane is also described. The quantification limits of the analytical procedure ranged from 30 to 60?ng?L^?1 for 500?mL of wastewater. The best recovery rates (72–102%) in spiked effluent samples were obtained with Phenomenex Strata-X? cartridges. Detection limits (S/N?=?3) were estimated at between 1 and 18?ng?L^?1. The reported GC–MS/MS method significantly reduces the strong matrix effects encountered with more expensive LC-MS/MS techniques. Application of the developed method showed that most selected analytes were detected at concentrations ranging from low µg?L^?1 to trace level ng?L^?1 in Montreal's wastewater treatment plant effluent and influent, as well as in the receiving waters at more than 8?km downstream of the effluent outfall. The rugged alternative analytical method is suitable for the simultaneous analysis of carbamazepine and pharmaceutical acidic residues in wastewater samples from influents and effluents that have undergone rough primary treatment.     

Application of DLLME to Isolation and Concentration of Non-Steroidal Anti-Inflammatory Drugs in Environmental Water Samples

Dispersive liquid–liquid microextraction (DLLME) coupled with liquid chromatography-tandem mass spectrometry detection was applied for determination of selected anti-inflammatory pharmaceuticals: ibuprofen, ketoprofen, naproxen and diclofenac. Development of DLLME procedure included optimisation of several important parameters such as kind and volume of extracting and dispersive solvents as well as sample pH. Under optimised conditions a two-step extraction with sonication was used. Chloroform was applied as the extracting and acetone as dispersing solvent. Calibration curves ranges were 1–500 μg L^?1 for naproxen and ibuprofen and 0.25–500 μg L^?1 for ketoprofen and diclofenac with correlation coefficients at least 0.997. Limits of quantitation were from 0.5 to 10 ng L^?1. The developed analytical method was employed for determination of ibubrofen, ketoprofen, naproxen and diclofenac in river and tap water samples. The results showed that DLLME is a simple, rapid and sensitive analytical technique for the pre-concentration of trace amounts of pharmaceuticals in environmental water samples.     

Synthesis and crystal structure of an O-silylated hexahomotriazacalix[3]arene

The first synthesis of an O-silylated derivative of a hexahomotriazacalix[3]arene has been achieved using 1-(trimethylsilyl)imidazole (TMSIM), 1,1,1,3,3,3-hexamethyldisilazane (HMDS), or bis(trimethylsilyl)trifluoroacetamide (BSTFA) in acetronitrile. The cone isomer was formed selectively using TMSIM and HMDS; whereas a cone/partial cone mixture was obtained using BSTFA.     

Simultaneous determination of pharmaceuticals, endocrine disrupting compounds and hormone in soils by gas chromatography-mass spectrometry

Analytical methods have been developed for simultaneous determination of six different pharmaceuticals and personal care products (PPCPs) (clofibric acid, ibuprofen, naproxen, ketoprofen, diclofenac, and triclosan), three endocrine disrupting compounds (EDCs) (4-tert-octylphenol, 4-n-nonylphenol, and bisphenol A (BPA)) and one estrogenic compound (estrone) in soil matrix. The soils were extracted by different solvents with the help of an ultrasonic treatment at 42 kHz, followed by a solid phase extraction (SPE) as a cleanup procedure. The purified extracts were derivatized with N-methyl-N-(tert-butyldimethylsilyl) trifluoroacetamide (MTBSTFA) and then analyzed by GC-MSD (SIM mode). The method was evaluated by testing the following variables: initial spiking levels, extraction solvents, solvent volumes, and soil types (sandy and clay soils). For 5 g of soil, four successive extraction steps with the mixture of acetone-ethyl acetate provided satisfactory recoveries. In the sandy soil, the recoveries of all the compounds were from 63.8 to 110.7% for the spiking level of 100 ng/g dry soil, and from 52.2 to 108.2% for 5 ng/g dry soil, respectively. Result was similar for the clay soil. The precision across all recoveries was high, suggesting that this method has a good reproducibility. The method was successfully employed to soil samples collected from a golf course irrigated with reclaimed wastewater in southern California, and resulted in the detection of clofibric acid, ibuprofen, naproxen, triclosan, bisphenol A, and estrone at ng per gram dry weight concentration levels. The method is robust and simple, and provides straightforward analyses of these current-emerging trace organic pollutants in solid matrices.     

Determination of naproxen in human plasma by GC–MS

This paper describes a GC–MS method for the determination of naproxen in human plasma. Naproxen and internal standard ibuprofen were extracted from plasma using a liquid–liquid extraction method. Derivatization was carried out using N‐methyl‐N‐(trimethylsilyl)trifluoroacetamide. The calibration curve was linear between the concentration range of 0.10–5.0 μg/mL. Intra‐ and interday precision values for naproxen in plasma were <5.14, and accuracy (relative error) was better than 4.67%. The extraction recoveries of naproxen from human plasma were between 93.0 and 98.9%. The LOD and LOQ of naproxen were 0.03 and 0.10 μg/mL, respectively. Also, this assay was applied to determine the pharmacokinetic parameters of naproxen in six healthy Turkish volunteers who had been given 220 mg naproxen.     

Trace analysis of acidic pharmaceutical residues in waters with isotope dilution gas chromatography-mass spectrometry via methylation derivatization

Acidic pharmaceutical residues are pollutants of emerging concern and are generally monitored by HPLC-MS/MS. However, due to the limited separation efficiency of HPLC column and lack of suitable mass transition for confirmation analysis, some interference may not be separated completely and differentiated from ibuprofen, which may cause the results with interference, especially in sample with complex matrix. The objective of this study is to develop a sensitive and reliable method for the determination of acidic pharmaceutical residues in water samples by GC-MS with better resolution by using methylation derivatization and isotope dilution techniques. TMSDM, a mild reagent, was used as the derivatization reagent coupling with the isotope dilution technique, for the first time, to improve the precision and accuracy of the analytical method to determine the pharmaceutical residues in water. The MDLs for the five acidic organic compounds: ibuprofen, gemfibrozil, naproxen, ketoprofen and diclofenac were from 0.7 to 1.1 ng/L, with recoveries ranging from 93 to 110%. Alternative to the HPLC-MS/MS method, the developed GC-MS protocols provides an additional option for the analysis of acidic pharmaceutical residues in water, with better separation efficiency in reducing interferences from complicated sample matrix, for determination of ibuprofen residues.     

Determination of pharmaceutical residues in waters by solid-phase extraction and large-volume on-line derivatization with gas chromatography-mass spectrometry

This work presents a modified method to analyze selected pharmaceutical residues (clofibric acid, ibuprofen, carbamazepine, naproxen, ketoprofen and diclofenac) in water samples. Various solid-phase extraction cartridges were investigated. The newly developed Oasis HLB (polystyrene-divinylbenzene-N-vinyl pyrrolidone terpolymer) solid-phase extraction (SPE) cartridge provides the optimal sample extraction results. The analytes were then identified and quantitatively determined by gas chromatography-mass spectrometry (GC-MS) via on-line derivatization in the injection-port using a large-volume (10 microl) sample injection with tetrabutylammonium (TBA) salts. This injection-port derivatization technique provides sensitivity, fast and reproducible results for pharmaceutical residues analysis. Mass spectra of butylated derivatives and tentative fragmentation profiles are proposed. Molecular ions and some characteristic ions were used as the quantitation ions to obtain maximum detection sensitivity and specificity. The quantitation limits of these compounds ranged from 1.0 to 8.0 ng/l in 500 ml tap water samples. Recovery of these residues in spiked various water samples ranged from 50 to 108% while RSD ranged from 1 to 10%. The selected analytes were detected in concentrations of 30 to 420 ng/l in wastewater treatment plant effluent and river water samples.