Determination of twenty pharmaceutical contaminants in soil using ultrasound-assisted extraction with gas chromatography-mass spectrometric detection.

In this paper, an analytical method for the simultaneous determination of twenty pharmaceuticals (eight non-steroidal anti-inflammatory drugs, five oestrogenic hormones, two antiepileptic drugs, two ß-blockers, and three antidepressants) in soils was developed. The optimal method included ultrasound-assisted extraction, a clean-up step on a silica gel column, derivatization using N,O-bis(trimethylsilyl)trifluoroacetamide (BSTFA) and 1% trimethylchlorosilane (TMCS) in pyridine and ethyl acetate (2:1:1, v/v/v) for 30 min at 60 °C, and determination by gas chromatography-mass spectrometry working in the selected ion monitoring mode. This affords good resolution, high sensitivity and reproducibility, and freedom from interferences even from complex matrices such as soils. The method detection limits ranged from 0.3 to 1.7 ng g-1, the intra-day precision represented as RSDs ranged from 1.1 to 10.0%, and the intra-day accuracy from 81.3 to 119.7%. The absolute recoveries of the target compounds were above 80%, except for valproic acid and diethylstilbestrol. The developed method was successfully applied in the analysis of the target compounds in soils collected in Poland. Among the 20 pharmaceuticals, 12 compounds were detected at least once in the soils. The determination of antiepileptic drugs, ß-blockers, and antidepressants was also performed for the first time.

Simultaneous determination of non-steroidal anti-inflammatory drugs and oestrogenic hormones in environmental solid samples.

Pharmaceuticals are continually being released into the environment. Because of their physical and chemical properties, many of them or their bioactive metabolites can accumulate in sediments, sludge and soils, and induce adverse effects in terrestrial organisms. However, due to the very limited methods permitting the detection of these low-level concentration compounds in such complex matrices, their concentrations in natural solids remain largely unknown. In this paper, an analytical method for the simultaneous determination of thirteen pharmaceuticals (eight non-steroidal anti-inflammatory drugs and five oestrogenic hormones) in solid matrices was developed. The proposed MAE-SPE-GC-MS(SIM) method has been successfully validated providing a linear response over a concentration range of 1(17)-1000(1200)ng/g, depending on the pharmaceuticals, with correlation coefficients above 0.991. The method detection limits were in the range of 0.3-5.7 ng/g, absolute recoveries above 50%, except estrone. The developed method was applied in the analysis of the target compounds in sediment, sludge and soils collected in Poland giving primary data on their concentrations in such matrices in Poland. The obtained results confirmed that the proposed method can be successfully used in the analysis of real environmental solid samples.

A new silylating reagent - dimethyl(3,3,3-trifluoropropyl)silyldiethylamine - for the derivatisation of non-steroidal anti-inflammatory drugs prior to gas chromatography-mass spectrometry analysis.

This paper discusses a new silylating reagent - dimethyl(3,3,3-trifluoropropyl)silyldiethylamine (DIMETRIS) - for the derivatisation of non-steroidal anti-inflammatory drugs (NSAIDs) prior to GC-MS analysis. DIMETRIS reacts with seven target compounds (diclofenac, ibuprofen, ketoprofen, naproxen, flurbiprofen and paracetamol, as well as salicylic acid, a degradation product of acetylsalicylic acid) at 30°C for 30min, producing mono-O-dimethyltrifluoropropylsilyl (mono-O-DMTFPS) derivatives. The mass spectra of these new derivatives are given and fully interpreted. The usefulness of mono-O-DMTFPS derivatives for the qualitative and quantitative analysis of NSAIDs using GC-MS is compared with that of trimethylsilyl and methyl analogues. Methyl derivatives are found to be less appropriate for this purpose because they yield the lowest detector responses during GC-MS measurements. Both silyl derivatives are more suitable for determining such NSAIDs, although the matrix effect with mono-O-DMTFPS derivatives is smaller. Finally, SPE-GC-MS(SIM) based on the derivatisation of NSAIDs by DIMETRIS is evaluated, validated and applied to the determination of these drugs in sea water (Baltic Sea) and wastewater samples collected in Poland. This work confirms that DIMETRIS is suitable for the trace analysis of NSAIDs in real samples and provides an interesting alternative to silylating and methylating reagents.

A new silylation reagent dimethyl(3,3,3-trifluoropropyl)silyldiethylamine for the analysis of estrogenic compounds by gas chromatography-mass spectrometry.

In this study we applied DIMETRIS (dimethyl(3,3,3-trifluoropropyl)silyldiethylamine), a new silylating reagent, to derivative natural estrogens such as estrone (E1), 17ß-estradiol (E2) and estriol (E3), as well as the synthetic 17α-ethinylestradiol (EE2) and the non-steroid diethylstilbestrol (DES). Its derivatizing properties were compared with those of the commonly used mixture of BSTFA (N,O-bis(trimethylsilyl)trifluoroacetamide)+1% trimethylchlorosilane (TMCS) and with MTBSTFA (N-tert-butyldimethylsilyl-N-methyltrifluoroacetamide). The use of DIMETRIS for the silylation all of them is reported for the first time. The nucleophilic properties of DIMETRIS were found to be superior to those of MTBSTFA, but slightly inferior to those of BSTFA. It was used to derivatize steroid (E1, E2, E3 and EE2) and non-steroid (DES) estrogens at 30°C prior to GC/MS analysis. These DMTFPS-derivatives exhibited good separation (low retention times despite the high molecular masses) and ionization properties in GC/MS analyses (the highest relative response factors for DMTFPS-derivatives among those tested). However, DIMETRIS and MTBSTFA (which produce mono-O-silyl derivatives of EE2) should not be used for the simultaneous analysis of EE2 and E1. Only a mixture of BSTFA+1% TMCS in pyridine, which generates the fully derivatized EE2 product (stable in GC injector), permits the determination of these two estrogenic compounds during one GC-MS run. On the other hand, because DIMETRIS requires a lower derivatization temperature than BSTFA, it could be very useful for the derivatization of thermally unstable estrogenic compounds. In the next step of this study, the SPE-GC-MS method based on DIMETRIS derivatization for the analysis of DES, E2 and E3 in aqueous samples was evaluated and validated. The MQL values: 1.4, 1.6 and 1.5ngL(-1) for DES, E2 and E3, respectively, proved its suitability to determine target compounds in environmental samples. Finally, the proposed method was successfully applied to the analysis of selected estrogenic compounds in real seawater and wastewater samples in Poland.

Chemometric optimization of derivatization reactions prior to gas chromatography-mass spectrometry analysis.

Derivatization is a methodological technique that can be used to make an organic compound more suitable for qualitative and/or quantitative analysis (e.g. pharmaceuticals). However, many analysts try to avoid this analytical procedure as it is time-consuming and labour-intensive. On the other hand, an inter-laboratory study demonstrated that with regard to sensitivity and measurement uncertainty, gas chromatography coupled to mass-spectrometry was superior to liquid chromatography coupled to mass spectrometry for the trace analysis of organic compounds in matrices of greater complexity. In our previous paper (Kumirska et al., J. Chemometr. 25 (2011) 636-643) we suggested using principal component analysis (PCA) to optimize the derivatization of six compounds (5 oestrogenic steroids and diethylstilbestrol) prior to GC-MS analysis. In the present work we applied a highly sophisticated model - 24 pharmaceuticals derived from six classes of drugs. The efficiency of different derivatization reactions was evaluated by PCA and compared with that obtained from cluster analysis (CA), the latter method being applied in this context for the first time. Derivatization using N,O-bis(trimethylsilyl)trifluoroacetamide (BSTFA) and 1% trimethylchlorosilane (TMCS) in pyridine and ethyl acetate (2:1:1, v/v/v) for 30min at 60°C was found to be optimal. The SPE-GC-MS method was also validated and successfully applied to the analysis of selected pharmaceuticals in wastewater and surface waters in Poland.

Simultaneous analysis of non-steroidal anti-inflammatory drugs and estrogenic hormones in water and wastewater samples using gas chromatography-mass spectrometry and gas chromatography with electron capture detection.

Non-steroidal anti-inflammatory drugs are the group of pharmaceuticals that is most often found in the environment, whereas estrogenic hormones are considered to be potent endocrine disruptors. However, the fate and persistence of these compounds in the environment are still unclear. In this study we propose two approaches for determining these compounds in environmental water samples: GC-MS using time windows and operating in selected ion-monitoring mode (SIM) and, for the first time, gas chromatography with electron capture detection (GC-ECD). The identification criteria of both methods fulfilled the requirements of Directive 2002/657/EC. The use of time windows improved the sensitivity of GC-MS measurements. In GC-MS analysis the pharmaceuticals were determined as trimethylsilyl, in GC-ECD as pentafluoropropionyl derivatives. The influence of such parameters as the type of reagent, type of solvent, reaction time, reaction temperature and microwave irradiation in a household microwave oven on the efficacy of silylation was investigated. Derivatization using N,O-bis(trimethylsilyl)trifluoroacetamide (BSTFA) and 1% trimethylchlorosilane (TMCS) in pyridine (1:1, v/v) for 30 min in 60 °C was found to be optimal. Optimization of the solid phase extraction procedure (SPE) confirmed that the application of Oasis HLB cartridges, the acidification of loading samples to pH2 and the use of methanol as eluent gave the best absolute recoveries (ARs) of the target compounds. The following ARs of all the compounds were achieved: 58.2-106.8% in influent wastewater, 77.8-103.4% in effluent wastewater and 81.2-101.9% in surface water samples. Validation of the SPE-GC-MS method enables 13 pharmaceuticals to be determined with MDLs between 3.3 and 343.6 ng/L, depending on the analytes and matrices. GC-ECD analysis enables the determination of 6 pharmaceuticals in surface water samples with MDLs between 0.7 and 5.4 ng/L. The proposed methods were successfully used for analyzing selected pharmaceuticals in wastewaters and river waters in Poland.

Matrix effects and recovery calculations in analyses of pharmaceuticals based on the determination of ß-blockers and ß-agonists in environmental samples.

In recent years substantial progress has been made in analytical methods for determining pharmaceutical residues in environmental samples. Although much work has attempted to establish the influence of sample matrix complexity on results through the determination of matrix effects (ME), extraction efficiency (EE) and absolute recovery of analytes (AR), comparison of these parameters is very complicated because different authors use different methods to obtain them. Moreover, there are few literature data describing the influence of aqueous matrices (tap water and waste water) on results obtained with GC-MS methods. For these reasons, the main aims of the present study were: (1) to critically review the determination of matrix effects and recovery parameters using the two most common techniques for analyzing drugs in environmental samples: gas and liquid chromatography coupled with mass spectrometry or tandem mass spectrometry (GC-MS, GC-MS/MS and LC-MS, LC-MS/MS); (2) to postulate a uniform method for determining ME, EE and AR using GC techniques; (3) to investigate the influence of different aqueous matrices on the solid-phase extraction, derivatization and final determination of drugs using GC. ß-Blockers and ß-agonists, drugs commonly found in the environment, were chosen as model compounds for this investigation. The values of ME, EE and AR obtained were compared with analogous (or similar) data obtained by other researchers using LC-MS measurements. All the results confirmed that GC-MS analyses are much less sensitive to the complexity of sample matrices than LC-MS, so GC-MS measurements appear to be a very good alternative to LC-MS methods of determining pharmaceutical residues in environmental samples.

Determination of ß-blockers and ß-agonists using gas chromatography and gas chromatography-mass spectrometry--a comparative study of the derivatization step.

There is a growing demand for the rapid screening of multiple ß-blockers and ß-agonists in a single analytical run in clinical toxicology, antidoping control, forensic and environmental science. Although GC-MS is very often used to determine pharmaceuticals from these groups of drugs, the literature data on the derivatization and MS analysis of mixtures of these compounds is limited. This paper compares and evaluates derivatization procedures for the determination of six ß-blockers (acebutolol, atenolol, metoprolol, nadolol, propranolol, pindolol) and two ß-agonists (salbutamol, terbutaline) using GC techniques. Nineteen different derivatizing reagents (nine of them used for the first time with almost all the drugs) were employed in order to obtain a single derivative for each target compound with the greatest effectiveness of this reaction. Trimethylsilylation, tert-butyldimethylsilylation, acylation (e.g. trifluoroacetylation), combined trimethylsilylation and acylation, and the formation of cyclized silyl derivatives were carried out and the mass spectra (EI, 70 eV) recorded. The influence of the reaction time and temperature on these procedures was investigated. Additionally, the effects of the type of solvent and the amount of added trimethylchlorosilane (TMCS) on the silylation of the target compounds using N,O-bis(trimethylsilyl)trifluoroacetamide (BSTFA) were tested. Among of the five mentioned above derivatization procedures applied - trimethylsilylation was found to be the most effective for derivatizing the analytes. The best results were obtained with a 1:1 (v/v) mixture of 99% BSTFA+1% TMCS and ethyl acetate at 60 °C for 30 min. The MS data for different types of ß-blocker and ß-agonist derivatives is presented. The information in this paper is valuable for scientists working on the determination of ß-blockers and ß-agonists in biological and environmental matrices.

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.