Magnetic micro‐solid‐phase extraction based on magnetite‐MCM‐41 with gas chromatography–mass spectrometry for the determination of antidepressant drugs in biological fluids

A new facile magnetic micro‐solid‐phase extraction coupled to gas chromatography and mass spectrometry detection was developed for the extraction and determination of selected antidepressant drugs in biological fluids using magnetite‐MCM‐41 as adsorbent. The synthesized sorbent was characterized by several spectroscopic techniques. The maximum extraction efficiency for extraction of 500 μg/L antidepressant drugs from aqueous solution was obtained with 15 mg of magnetite‐MCM‐41 at pH 12. The analyte was desorbed using 100 μL of acetonitrile prior to gas chromatography determination. This method was rapid in which the adsorption procedure was completed in 60 s. Under the optimized conditions using 15 mL of antidepressant drugs sample, the calibration curve showed good linearity in the range of 0.05–500 μg/L (r ² = 0.996–0.999). Good limits of detection (0.008–0.010 μg/L) were obtained for the analytes with good relative standard deviations of <8.0% (n  = 5) for the determination of 0.1, 5.0, and 500.0 μg/L of antidepressant drugs. This method was successfully applied to the determination of amitriptyline and chlorpromazine in plasma and urine samples. The recoveries of spiked plasma and urine samples were in the range of 86.1–115.4%. Results indicate that magnetite micro‐solid‐phase extraction with gas chromatography and mass spectrometry is a convenient, fast, and economical method for the extraction and determination of amitriptyline and chlorpromazine in biological samples.     

Determination of N‐nitrosamines in cosmetic products by vortex‐assisted reversed‐phase dispersive liquid–liquid microextraction and liquid chromatography with mass spectrometry

A new analytical method for the simultaneous determination of trace levels of seven prohibited N‐nitrosamines (N‐nitrosodimethylamine, N‐nitrosoethylmethylamine, N‐nitrosopyrrolidine, N‐nitrosodiethylamine, N‐nitrosopiperidine, N‐nitrosomorpholine, and N‐nitrosodiethanolamine) in cosmetic products has been developed. The method is based on vortex‐assisted reversed‐phase dispersive liquid–liquid microextraction, which allows the extraction of highly polar compounds, followed by liquid chromatography with mass spectrometry. The variables involved in the extraction process were studied to obtain the highest enrichment factor. Under the selected conditions, 75 μL of water as extraction solvent was added to 5 mL of n‐hexane sample solution and assisted by vortex mixing during 30 s to form the cloudy solution. The method was successfully validated showing good linearity (0.5–50 ng/mL), enrichment factors up to 65 depending on the target compound, limits of detection values of 1.8–50 ng/g, and good repeatability (RSD < 9.8%). Finally, the proposed method was applied to different cosmetic samples. Quantitative relative recovery values (80–113%) were obtained, thus showing that matrix effects were negligible. The achieved analytical features of the proposed method, besides of its simplicity and affordability, make it useful to perform the quality control of cosmetic products to ensure the safety of consumers.     

Simultaneous detection of three antiviral and four antibiotic compounds in source‐separated urine with liquid chromatography

An analytical method for the simultaneous screening of three antiviral agents (nevirapine, zidovudine, lamivudine), four antibiotics (sulfamethoxazole, trimethoprim, ciprofloxacin, rifampicin) and one reference compound (carbamazepine) in human urine was developed. Separation was achieved with a Kinetex XB‐C₁₈ (75 × 4.6 mm, 2.6 μm) column after the extraction of pharmaceuticals from urine with SPE. Gradient elution with a mobile phase consisting of acetonitrile and 10 mM KH₂PO₄ (pH 2.5), and diode array detection with monitoring at 210 and 264 nm was applied. The developed method was validated in terms of selectivity, linearity, stability and sensitivity. Repeatability (n = 3) and between‐day precision (n = 3) revealed RSD <5%. The detection limits were estimated as 0.02–0.54 g/L (depending on compound). The method was validated for human urine and successfully applied to the simultaneous quantification of selected compounds. Strata‐X cartridges provided good recoveries ranging from 81 to 109%. The limits of detection for urine varied between 0.04 and 1.61 g/L. The method is suitable for the fast determination of selected pharmaceuticals from source‐separated urine samples for further environmental risk assessment and degradation potential evaluation. It provides a way to enhance safe nutrient recycling from wastewater streams and promotes the safe use of urine as fertiliser.     

Simultaneous separation and determination of 20 potential adulterant antigout and antiosteoporosis pharmaceutical compounds in herbal food products using LC with electrospray ionization MS/MS and LC with quadrupole‐time‐of‐flight MS

An analytical method for the simultaneous and reliable determination of 20 antigout and antiosteoporosis pharmaceutical compounds in adulterated health food products was developed using liquid chromatography with electrospray ionization tandem mass spectrometry and liquid chromatography with quadrupole‐time‐of‐flight mass spectrometry. The method was validated through the determination of specificity, linearity, limit of detection, and limit of quantification, method detection limit, method quantitation limit, precision, accuracy, recovery, and stability. The matrix effect was also determined. The validation results of the developed method are as follows: for solid and liquid blank samples, limits of detection ranged from 0.05 to 5.00 ng/mL and limits of quantification ranged from 0.15 to 15.00 ng/mL. Linearity was acceptable, and the correlation coefficients (R²) were ≥0.99 for all target compounds. Both intra and interday precision were less than 9.16% RSD, and accuracies ranged from 95.31 to 116.68%. Mean recoveries for different types of dietary supplements classified as powders, liquids, tablets, and capsules were found to be 80.81 to 117.62% with less than 15.00% relative standard deviation. The stability of the standard mixture solution was less than 11.72% relative standard deviation after 48 h. By the proposed method, the presence of dexamethasone was determined in seized herbal food products at concentrations that ranged from 126 to 215 µg/g.     

高效液相色谱-质谱法测定性保健品中脱水吗啡、西地那非、前列地尔

建立了高效液相色谱-电喷雾电离质谱法同时测定性保健品中违禁药物脱水吗啡、西地那非和前列地尔的分析方法。样品用甲醇超声提取,用Zorbax Eclipse XDB-C18柱分离,以乙腈-0.5%甲酸水溶液作为流动相,以保留时间和质荷比对分离出的组分予以定性确证,用峰面积进行定量。结果表明,脱水吗啡、西地那非和前列地尔的线性范围分别为50.0~5000.0 μg/L,10.0~1000.0 μg/L和40.0~4000.0 μg/L,检出限(以信噪比为3计)分别为20.0,4.0和10.0 μg/L。样品的加标平均回收率为89%~95%,相对标准偏差为9.5%~11%。该方法简便、快速、灵敏,适用于含中药成分的性保健品中这3种药物的同时分析。     

High‐performance liquid chromatography with diode array detection method for the simultaneous determination of seven selected phosphodiesterase‐5 inhibitors and serotonin reuptake inhibitors used as male sexual enhancers

This work presents a simple, sensitive and generic high‐performance liquid chromatography with diode array detection method for the simultaneous determination of seven drugs prescribed for the treatment of erectile dysfunction and premature ejaculation. Investigated drugs include the phosphodiesterase‐5 inhibitors: sildenafil, tadalafil, and vardenafil, in addition to the selective serotonin reuptake inhibitors: dapoxetine, duloxetine, fluoxetine, and paroxetine. The drugs were separated using a Waters C8 column (4.6 × 250 mm, 5 μm) with the mobile phase consisting of phosphate buffer pH 3, acetonitrile and methanol in the ratio 60:33:7. The flow rate was 1.2 mL/min, and quantification was based on measuring peak areas at 225 nm. Peaks were perfectly resolved with retention times 3.3, 3.9, 6.4, 7.5, 9.5, 10.7, and 13.4 min for vardenafil, sildenafil, paroxetine, duloxetine, dapoxetine, fluoxetine, and tadalafil, respectively. The developed method was validated with respect to system suitability, linearity, ranges, accuracy, precision, robustness, and limits of detection and quantification. The proposed method showed good linearity in the ranges 5–500, 2–200, 2–200, 3–300, 1.5–150, 2–200, and 2–200 μg/mL for sildenafil, tadalafil, vardenafil, dapoxetine, duloxetine fluoxetine, and paroxetine, respectively. The limits of detection were 0.18–0.38 μg/mL for the analyzed compounds. The applicability of the proposed method to real life situations was assessed through the analysis of commercial tablets, and satisfactory results were obtained.     

Development of an ASE‐GC‐MS/MS method for detecting dinitolmide and its metabolite 3‐ANOT in eggs

An accelerated solvent extraction coupled with gas chromatography‐tandem mass spectrometry (ASE‐GC‐MS/MS) method for detecting dinitolmide residue and its metabolite (3‐amino‐2‐methyl‐5‐nitrobenzamide, 3‐ANOT) in eggs was developed and optimized. The samples were extracted using ASE with acetonitrile as the extractant and were purified by passage through a neutral alumina solid‐phase extraction column. Then, the samples were analyzed using the GC‐MS/MS method. The optimized method parameters were validated according to the requirements set forth by the European Union and the Food and Drug Administration. The average recoveries of dinitolmide and 3‐ANOT from eggs (egg white, egg yolk, and whole egg) at the limit of quantification (LOQ), 0.5 maximum residue limit (MRL), 1 MRL, and 2 MRL were 82.74% to 87.49%, the relative standard deviations (RSDs) were less than 4.63%, and the intra‐day RSDs and the inter‐day RSDs were 2.96% to 5.21% and 3.94% to 6.34%, respectively. The limits of detection and the LOQ were 0.8 to 2.8 μg/kg and 3.0 to 10.0 μg/kg, respectively. The decision limits (CC_α) were 3001.69 to 3006.48 μg/kg, and the detection capabilities (CC_β) were 3001.74 to 3005.22 μg/kg. Finally, the new method was successfully applied to the quantitative determination of dinitolmide and 3‐ANOT in 50 commercial eggs from local supermarkets.     

A gas chromatography/mass spectrometry method for the determination of sildenafil,vardenafil and tadalafil and their metabolites in human urine

Sildenafil (SDF), vardenafil (VDF) and tadalafil (TDF) are phosphodiesterase type 5 enzyme inhibitors (PDE5Is), used in the treatment of erectile disorders and to improve breathing efficiency in pulmonary hypertension. The increasing incidence of their use among young athletes has drawn the attention of the anti‐doping authorities to the possible abuse of PDE5Is by athletes due to their pharmacological activities. This paper describes a method for the determination in urine of PDE5Is and their metabolites by gas chromatography/mass spectrometry (GC/MS) after liquid/liquid extraction of the analytes from urine and derivatisation to obtain trimethylsilyl derivatives. The metabolic profile was studied on real samples collected from subjects taking PDE5Is (Viagra®, Levitra® or Cialis®); the main urinary metabolites were identified and their MS fragmentation characterized. The sample pre‐treatment and GC/MS conditions for the detection of the metabolites have been optimised. A method for their preliminary screening and subsequent confirmation is described that takes into account the general requirements of a routine doping analysis to be used for the screening of large numbers of samples. The main metabolites identified can be included in a general purpose screening method and all the metabolites in a more specific confirmation method. The method developed has been applied for the screening of PDE5Is in 5000 urine samples. Based on the obtained results, the proposed method appears to be of practical use in analytical and forensic toxicology, including doping analysis. Copyright © 2010 John Wiley & Sons, Ltd.     

Determination of trace hydroxyl polycyclic aromatic hydrocarbons in urine using graphene oxide incorporated monolith solid‐phase extraction coupled with LC‐MS/MS

The biomonitoring of hydroxy polycyclic aromatic hydrocarbons in urine, as a direct way to access multiple exposures to polycyclic aromatic hydrocarbons, has raised great concerns due to their increasing hazardous health effects on humans. Solid‐phase extraction is an effective and useful technique to preconcentrate trace analytes from biological samples. Here, we report a novel solid‐phase extraction method using a graphene oxide incorporated monolithic syringe for the determination of six hydroxy polycyclic aromatic hydrocarbons in urine coupled with liquid chromatography‐tandem mass spectrometry. The effect of graphene oxide amount, washing solvent, eluting solvent, and its volume on the extraction performance were investigated. The fabricated monoliths gave higher adsorption efficiency and capacity than the neat polymer monolith and commercial C₁₈ sorbent. Under the optimum conditions, the developed method provided the detection limits (S/N = 3) of 0.02–0.1 ng/mL and the linear ranges of 0.1–1500 ng/mL for six analytes in urine sample. The recoveries at three spiked levels ranged from 77.5 to 97.1%. Besides, the intra column‐to‐column (n = 3) and inter batch‐to‐batch (n = 3) precisions were ≤ 9.8%. The developed method was successfully applied for the determination of hydroxy polycyclic aromatic hydrocarbons in urine samples of coke oven workers.     

Application of a LC–MS/MS method developed for the determination of p‐phenylenediamine,N‐acetyl‐p‐phenylenediamine and N,N‐diacetyl‐p‐phenylenediamine in human urine specimens

Cases of poisoning by p‐phenylenediamine (PPD) are detected sporadically. Recently an article on the development and validation of an LC–MS/MS method for the detection of PPD and its metabolites, N‐acetyl‐p‐phenylenediamine (MAPPD) and N,N‐diacetyl‐p‐phenylenediamine (DAPPD) in blood was published. In the current study this method for detection of these compounds was validated and applied to urine samples. The analytes were extracted from urine samples with methylene chloride and ammonium hydroxide as alkaline medium. Detection was performed by LC–MS/MS using electrospray positive ionization under multiple reaction‐monitoring mode. Calibration curves were linear in the range 5–2000 ng/mL for all analytes. Intra‐ and inter‐assay imprecisions were within 1.58–9.52 and 5.43–9.45%, respectively, for PPD, MAPPD and DAPPD. Inter‐assay accuracies were within ?7.43 and 7.36 for all compounds. The lower limit of quantification was 5 ng/mL for all analytes. The method, which complies with the validation criteria, was successfully applied to the analysis of PPD, MAPPD and DAPPD in human urine samples collected from clinical and postmortem cases.     

Validation of a new high‐throughput method to determine urinary S‐phenylmercapturic acid using low‐temperature partitioning extraction and ultra high performance liquid chromatography–mass spectrometry

A new highly sensitive and environmentally friendly analytical method, using low‐temperature partition extraction and ultra‐high‐performance liquid chromatography with tandem mass spectrometry, without the use of a labeled analyte, was developed and validated to determine and quantify urinary S‐phenylmercapturic acid in urine samples. The World Health Organization, in its guidelines for air quality in Europe, recognizes that benzene is carcinogenic to humans and there is no safe level of exposure. Urinary S‐phenylmercapturic acid is a sensitive and specific biological marker of exposure to benzene. The new analytical method, extraction, and analysis, were linear in the working range between 0.1 and 200.0 μg/L, precise (relative standard deviation lower than 6.0%), accurate (97.0–105.0%), and sensitive. The method's limits of detection and quantification were 0.02 and 0.084 μg/L, respectively. The recovery with the low‐temperature partition extraction was 96.1%, with relative standard deviation less than 3.8%. The method is simple, accurate, and reproducible, and has been successfully applied in the evaluation of nonoccupational exposure to benzene, by urinary S‐phenylmercapturic acid in urine samples.     

Separation and quantification of imidazoles in atmospheric particles using LC–Orbitrap‐MS

A method using ultra‐high performance liquid chromatography coupled to a high resolution Orbitrap mass spectrometer was developed to identify and quantify imidazoles in aqueous extracts of aerosol particles. The aqueous particle extract was used without further enrichment or sample clean‐up. Five columns were tested for efficient separation of ten imidazoles and the Acquity HSS T3 column was chosen for further optimization. Low limits of detection (<25 nM) and good intraday and interday repeatability (<1.6 and <6%, respectively) were achieved. Investigation of matrix effects showed that external calibration is applicable when the loading of organic carbon in the sample is below 10 µg m^?3. The developed method was applied to ten real samples, and six out of the ten test imidazoles were successfully quantified, while six further imidazoles were qualitatively identified, among them 4‐imidazolecarboxaldehyde and 4‐methyl‐5‐imidazolecarboxaldehyde. Advantages of the method are the minimal sample preparation, the short run time for each sample, and the low detection limits. These allow for a fast and reliable quantification of imidazoles even in a large number of aqueous particle extract samples.     

Simple and sensitive determination of malondialdehyde in human urine and saliva using UHPLC–MS/MS after derivatization with 3,4‐diaminobenzophenone

Malondialdehyde has been used as a biomarker for lipid peroxidation in biological samples. An ultra‐high performance liquid chromatography with tandem mass spectrometry method was developed to determine the levels of malondialdehyde in human urine and saliva samples. To select the optimum derivatization reagent from four diamino compounds, the reactivity and sensitivity of their derivatives were compared, and 3,4‐diaminobenzophenone was selected. The optimum reaction conditions for malondialdehyde with 3,4‐diaminobenzophenone were as follows: a reagent dosage of 50 mg/L, pH of 4, and reaction for 30 min at 50°C. The formed derivative product was analyzed using ultra‐high performance liquid chromatography with tandem mass spectrometry without additional extraction or concentration steps. In the optimal conditions, the method was used to determine malondialdehyde concentration in human urine and saliva samples. The limits of quantification for malondialdehyde in biological samples were over a concentration range of 0.1–0.3 μg/L. Additionally, the calibration curve showed a linearity greater than r ² = 0.997. The method was used to analyze 14 human urine and saliva samples from healthy volunteers. Malondialdehyde was detected in the concentration range of 1.7–33.6 μg/g creatinine in all human urine samples and 0.1–1.3 μg/L in all human saliva samples.     

Application of ultrasound‐assisted liquid–liquid microextraction coupled with gas chromatography and mass spectrometry for the rapid determination of synthetic cannabinoids and metabolites in biological samples

The constant emergence of new psychoactive substances is a challenge to clinical and forensic toxicologists who need to constantly update analytical techniques to detect them. A large portion of these substances are synthetic cannabinoids. The aim of this study was to develop a rapid and simple method for the determination of synthetic cannabinoids and their metabolites in urine and blood using gas chromatography–mass spectrometry. The method involves an ultrasound‐assisted dispersive liquid–liquid microextraction that implies a rapid procedure, giving excellent extraction efficiencies with minimal use of toxic solvents. This is followed by silylation and analysis with gas chromatography–mass spectrometry. The chromatographic method allows for the separation and identification of 29 selected synthetic cannabinoids and some metabolites. The method was validated on urine and blood samples with the ability to detect and quantify all analytes with satisfactory limits of detection (from 1 to 5 ng/mL), limits of quantification (5 ng/mL), and selectivity and linearity (in the range of 5–200 ng/mL). The developed assay is highly applicable to laboratories with limited instrumental availability, due to the use of efficient and low‐cost sample preparation and instrumental equipment. The latter may contribute to enhance the detection of new psychoactive substances in clinical and forensic toxicology laboratories.     

Determination of betaine,l‐carnitine,and choline in human urine using a self‐packed column and column‐switching ion chromatography with nonsuppressed conductivity detection

A simple method for the determination of betaine, l ‐carnitine, and choline in human urine was developed based on column‐switching ion chromatography coupled with nonsuppressed conductivity detection by using a self‐packed column. A pretreatment column (50 mm × 4.6 mm, id) packed with poly(glycidyl methacrylate‐divinylbenzene) microspheres was used for the extraction and cleanup of analytes. Chromatographic separation was achieved within 10 min on a cationic exchange column (150 mm × 4.6 mm, id) using maleic anhydride modified poly(glycidyl methacrylate‐divinylbenzene) as the particles for packing. The detection was performed by ion chromatography with nonsuppressed conductivity detection. Parameters including column‐switching time, eluent type, flow rates of eluent, and interfering effects were optimized. Linearity (r ² ≥ 0.99) was obtained for the concentration range of 0.50–100, 0.75–100, and 0.25–100 μg/mL for betaine, l ‐carnitine, and choline, respectively. Detection limits were 0.12, 0.20, and 0.05 μg/mL for betaine, l ‐carnitine, and choline, respectively. The intra‐ and interday accuracy and precision for all quality controls were within ±10.11%. Satisfactory recovery was observed between 92.5 and 105.0%. The validated method was successfully applied for the determination of betaine, l ‐carnitine, and choline in urine samples from healthy people.     

Quantitative determination of metformin,glyburide and its metabolites in plasma and urine of pregnant patients by LC‐MS/MS

This report describes the development and validation of an LC‐MS/MS method for the quantitative determination of glyburide (GLB), its five metabolites (M1, M2a, M2b, M3 and M4) and metformin (MET) in plasma and urine of pregnant patients under treatment with a combination of the two medications. The extraction recovery of the analytes from plasma samples was 87–99%, and that from urine samples was 85–95%. The differences in retention times among the analytes and the wide range of the concentrations of the medications and their metabolites in plasma and urine patient samples required the development of three LC methods. The lower limit of quantitation (LLOQ) of the analytes in plasma samples was as follows: GLB, 1.02 ng/mL; its five metabolites, 0.100–0.113 ng/mL; and MET, 4.95 ng/mL. The LLOQ in urine samples was 0.0594 ng/mL for GLB, 0.984–1.02 ng/mL for its five metabolites and 30.0 µg/mL for MET. The relative deviation of this method was <14% for intra‐day and inter‐day assays in plasma and urine samples, and the accuracy was 86–114% in plasma, and 94–105% in urine. The method described in this report was successfully utilized for determining the concentrations of the two medications in patient plasma and urine. Copyright © 2014 John Wiley & Sons, Ltd.     

Simultaneous analysis of multiple urinary biomarkers for the evaluation of oxidative stress by automated online in‐tube solid‐phase microextraction coupled with negative/positive ion‐switching mode liquid chromatography–tandem mass spectrometry

This study described an automated online method for the simultaneous determination of 8‐isoprostane, 8‐hydroxy‐2′‐deoxyguanosine, and 3‐nitro‐l ‐tyrosine in human urine. The method involves in‐tube solid‐phase microextraction using a Carboxen 1006 PLOT capillary column as an extraction device, followed by liquid chromatography with tandem mass spectrometry using a CX column and detection in the negative/positive switching ion‐mode by multiple reaction monitoring. Using their stable isotope‐labeled internal standards, each of these oxidative stress biomarkers showed good linearity from 0.02 to 2.0 ng/mL. Their detection limits (S/N = 3) were 3.4–21.5 pg/mL, and their intra‐ and inter‐day precisions (relative standard deviations) were >3.9 and 6.5% (n = 5), respectively. This method was applied successfully to the analysis of urine samples, without any other pretreatment and interference peaks.     

Surfactant‐assisted dispersive liquid–liquid microextraction combined with field‐amplified sample stacking in capillary electrophoresis for the determination of mexiletine and lidocaine

A sensitive method for the determination of mexiletine and lidocaine using surfactant‐assisted dispersive liquid–liquid microextraction coupled with capillary electrophoresis was developed. Triton X‐100 and dichloromethane were used as the dispersive agent and extraction solvent, respectively. After the extraction, mexiletine and lidocaine were analyzed using capillary electrophoresis with ultraviolet detection. The detection sensitivity was further enhanced through the use of field‐amplified sample stacking. Under optimal extraction and stacking conditions, the calibration curves were linear over a concentration range of 0.05–1.00 μM for mexiletine and 0.03–1.00 μM for lidocaine. The limits of detection (signal‐to‐noise ratio of 3) were 0.01 and 0.01 μM for mexiletine and lidocaine, respectively. An approximately 1141‐ to 1250‐fold improvement in sensitivity was observed for the two analytes compared with the injection of a standard solution without the surfactant‐assisted dispersive liquid–liquid microextraction and field‐amplified sample stacking procedures. This developed method was successfully applied to the determination of mexiletine and lidocaine in human urine and serum samples. Both precision and accuracy for urine and serum samples were less than 8.7 and 6.7%, respectively. The recoveries of the two analytes from urine and serum samples were 54.7–64.9% and 16.1–56.5%, respectively.     

Structure elucidation of phototransformation products of unapproved analogs of the erectile dysfunction drug sildenafil in artificial freshwater with UPLC‐Q Exactive‐MS

In this study, four unapproved analogues of Sildenafil (SDF) were photodegraded under synthetic sunlight in artificial freshwater. Homosildenafil (H‐SDF), hydroxyhomo‐sildenafil (HH‐SDF), norneosildenafil (NR‐SDF) and thiosildenafil (T‐SDF) were selected because they are frequently detected as adulterants in natural herbal products. Using UPLC‐Orbitrap (Q Exactive)‐MS, six photoproducts common to H‐SDF, HH‐SDF and T‐SDF and nine unique transformation products of different molecular weights were identified based on their high‐resolution (+)ESI product ion spectra. Mass spectral analysis of deuterated H‐SDF, labeled on the N‐ethyl group, allowed to gain mechanistic insight into the fragmentation pathway of the substituted piperazine ring and to support the postulated photoproduct structures. The mass spectral fragmentation confirmed the stepwise destruction of the piperazine ring eventually producing a sulfonic acid derivative (C₁₇H₂₀N₄O₅S: 392.1151 Da). In contrast, the photodegradation of NR‐SDF, which lacks a piperazine ring in its structure, formed only two prominent photoproducts originating from N,N‐dealkylation of the sulfonamide followed by hydrolysis. The current work constitutes the first study on the photodegradation of analogs of erectile dysfunction drugs and the first detection of two transformation products (m/z 449 and 489) in environmental samples. Copyright © 2014 John Wiley & Sons, Ltd.     

A new and fast strategy based on semiautomatic microextraction by packed sorbent followed by ultra high performance liquid chromatography for the analysis of drugs and their metabolites in human urine

A novel analytical approach has been developed for the determination of selected drugs (milrinone, enalapril, carvedilol, spironolactone, acenocumarol, ticlopidine, cilazapril) and their metabolites (2‐oxoticlopidine, cilazaprilat, canrenone, 5′‐hydroxycarvedilol, O‐desmethyl‐carvedilol, enalaprilat) in human urine, based on a miniaturized extraction technique; semiautomatic microextraction by packed sorbent, using a new digitally controlled syringe, followed by ultra high pressure liquid chromatography separation combined with UV detection. During method optimization, the extraction parameters as the type of sorbent material, type and volume of elution solution, number of extraction cycles, volume and pH of sample, type and volume of washing solution were studied. The chromatographic separation of the target analytes was performed with a core–shell analytical column using 0.05% trifluoroacetic acid in water and acetonitrile in gradient elution mode. The limits of quantification ranged from 0.016 to 0.045 μg/mL. Under the optimized conditions, extraction efficiency was higher than 70.1% for drugs and their metabolites. Due to its simplicity and speed, this method was successfully applied to the quantitation of selected compounds in urine samples.