Oxidized Multiwalled Carbon Nanotubes as an SPME Fiber Coating for Rapid LC–UV Analysis of Benzimidazole Fungicides in Water

The potential of oxidized multiwalled carbon nanotubes as a fiber coating for solid-phase microextraction of carbendazim, thiabendazole, and thiophanate-methyl from aqueous solution has been investigated, and the mechanism of adsorption has been explored. When an analytical method combining SPME with high-performance liquid chromatography was applied to real environmental water samples, recoveries of the spiked compounds was 75.7–104.5%, the linear range was 5–500 ng mL^?1, the squared correlation coefficients (r ²) were from 0.9978 to 0.9984, LOD were from 0.3 to 1.5 ng mL^?1, and RSD were from 2.3 to 10.5%.     

Simultaneous Determination of Tamsulosin and Dutasteride in Human Plasma by LC–MS–MS

A sensitive and selective liquid chromatographic tandem mass spectrometric (LC–MS–MS) method was developed for simultaneous identification and quantification of tamsulosin and dutasteride in human plasma, which was well applied to clinical study. The method was based on liquid–liquid extraction, followed by an LC procedure with a Gemini C-18, 50 mm × 2.0 mm (3 μm) column and using methanol:ammonium formate (97:3, v/v) as the mobile phase. Protonated ions formed by a turbo ionspray in positive mode were used to detect analytes and internal standard. MS–MS detection was by monitoring the fragmentation of 409.1 → 228.1 (m/z) for tamsulosin, 529.3 → 461.3 (m/z) for dutasteride and 373.2 → 305.3 (m/z) for finasteride (IS) on a triple quadrupole mass spectrometer. The lower limit of quantification for both tamsulosin and dutasteride was 1 ng mL^?1. The proposed method enables the unambiguous identification and quantification of tamsulosin and dutasteride for clinical drug monitoring.     

Simultaneous Determination of Atenolol and Chlorthalidone by LC–MS–MS in Human Plasma

A simple, sensitive, selective and rapid liquid chromatography–tandem mass spectrometry method was developed and validated for the simultaneous separation and quantitation of atenolol and chlorthalidone in human plasma using metoprolol and hydrochlorothiazide as internal standard. Following solid phase extraction, the analytes were separated by an isocratic mobile phase on a reversed-phase C₁₈ column and analyzed by MS in the multiple reaction-monitoring mode (atenolol in positive and chlorthalidone in the negative ion mode). The limit of quantitation for this method was 10 and 15 ng mL^?1 and the linear dynamic range was generally 10–2,050 ng mL^?1 and 15–3,035 ng mL^?1 for atenolol and chlorthalidone, respectively.     

Simultaneous Determination of Ten Estrogens and their Metabolites in Waters by Improved Two-Step SPE Followed by LC–MS

Ten highly potent estrogens including estrone (E₁), 17β-estradiol (E₂), estriol (E₃), 4-hydroxyestrone (4-OHE₁), 2-hydroxyestradiol (2-OHE₂), 16α-hydroxyestrone (16α-OHE₁), 2-methoxyestrone (2-MeO-E₁), 2-methoxyestradiol (2-MeO-E₂), diethylstilbestrol (DES), 17α-ethynylestradiol (EE₂) were identified and quantified by solid-phase extraction followed by liquid chromatography–mass spectrometry. An improved two-step SPE process was employed in this work. C18 cartridge was used for both enrichment of all target estrogens and retention of some nonpolar impurities, and then a polar florisil cartridge was subsequently used to separate the interested estrogens from the polar impurities. After this pretreatment for water samples, the results showed clean chromatograms without interference from matrix effects. Besides, this method was accurate (recovery percentages between 70.4 and 106.8% for river water and 73.4 and 101.3% for raw sewage, except 4-OHE₁ and 2-OHE₂), and precise (RSD varying between 1.3 and 17.8% for river water and 3.4 and 16.7% for raw sewage). In the optimized condition, this method was used to verify the presence of the target analytes in the Qinghe River and influent of sewage treatment plant in the northwest of Beijing, China. Some estrogens were detected in the river water and sewage water samples at a relatively high concentration. The developed method proved to be effective for analyzing estrogen compounds in complex matrices. Moreover, the achieved results demonstrated that a great concern should be addressed to the potential risk of the presence of estrogens in the aquatic environment.     

Simultaneous Determination of Anabolic Androgenic Steroids and Their Esters in Hair by LC–MS–MS

A liquid chromatographic-tandem mass spectrometric method for the simultaneous determination of anabolic androgenic steroids and their esters in hair has been developed. The hair sample was treated with methanol to extract the esters, followed by alkaline digestion for optimum recovery of the anabolic androgenic steroids. After liquid–liquid extractions, the extract was dried, redissolved and analyzed by multiple reaction monitoring with a quadrupole mass spectrometer. The lower limits of detection ranged from 0.001 to 0.020 ng mg^?1 for the 21 analytes. The applicability of the method was demonstrated using guinea pig hair samples gained from controlled experiments.     

Simultaneous Determination of Paracetamol and Caffeine in Human Plasma by LC–ESI–MS

A rapid, selective and convenient liquid chromatography–mass spectrometric method for the simultaneous determination of paracetamol and caffeine in human plasma was developed and validated. Analytes and theophylline [internal standard (I.S.)] were extracted from plasma samples with diethyl ether-dichloromethane (3:2, v/v) and separated on a C₁₈ column (150 × 4.6 mm ID, 5 μm particle size, 100 Å pore size). The mobile phase consisted of 0.2% formic acid–methanol (60:40, v/v). The assay was linear in the concentration range between 0.05 and 25 μg mL^?1 for paracetamol and 10–5,000 ng mL^?1 for caffeine, with the lower limit of quantification of 0.05 μg mL^?1 and 10 ng mL^?1, respectively. The intra- and inter-day precision for both drugs was less than 8.1%, and the accuracy was within ±6.5%. The single chromatographic analysis of plasma samples was achieved within 4.5 min. This validated method was successfully applied to study the pharmacokinetics of paracetamol and caffeine in human plasma.     

Determination of Pitavastatin in Human Plasma by LC–MS–MS

A simple and rapid LC–MS–MS assay was developed and validated for the quantitative determination of pitavastatin in human plasma. Sample pretreatment involved simple protein precipitation by addition of acetonitrile. Separation was on an Agilent 1.8 μm Zorbax SB-C18 column (150 mm × 4.6 mm) at 25 °C using isocratic elution with methanol–0.1% formic acid in water (85:15, v/v) at a flow rate of 0.4 mL min^?1. Detection was performed using electrospray ionization in positive ion multiple reaction monitoring mode by monitoring the ion transitions m/z 422.0 → 290.1 for pitavastatin, and m/z 330.1 → 192.1 for paroxetine (IS). LC–MS–MS was found to improve the quantitation of pitavastatin in plasma and was successfully applied in pharmacokinetic studies.     

Simultaneous Determination of Levodopa, Benserazide and 3-O-Methyldopa in Human Serum by LC–MS–MS

For the first time a sensitive, specific and rapid LC–MS–MS assay is presented for the simultaneous determination of levodopa (L-DP), 3-O-methyldopa (3-OMD) and benserazide (BSZ) in human serum. The three compounds were extracted from human serum by protein precipitation followed by dilution of the supernatant with aqueous formic acid. In serum, linearity was observed between 50 and 1,000 ng mL^?1 of L-DP, 3-OMD and BSZ, respectively. Intra-day and inter-day RSD values were below 10.56 and 6.22% at concentrations of 120, 360 and 720 ng mL^?1. The presented method showed excellent specificity and sensitivity compared with other methods reported. It was applied to a pharmacokinetic study and demonstrated its applicability to pre-clinical and clinical pharmacological research.     

Simultaneous Determination of Ramipril and Its Active Metabolite Ramiprilat in Human Plasma by LC–MS–MS

A selective, rapid and sensitive liquid chromatography tandem mass spectrometry method has been developed for the simultaneous determination of ramipril and ramiprilat in human plasma using enalapril as the internal standard via one-step extraction with ethyl acetate under acidic condition. The analysis was carried out on a Diamonsil C₁₈ column (150 mm × 4.6 mm i.d., 5 μm) with a mobile phase consisting of 1% formic acid-acetonitrile (25:75, v/v) at a constant flow rate of 0.5 mL min^?1. The detection was performed on a triple-quadruple tandem mass spectrometer by selective reaction monitoring mode via electrospray ionization. Linear calibration curves of ramipril and ramiprilat were obtained in the concentration range of 0.107–107.0 and 0.262–105.0 ng mL^?1, respectively. The intra- and inter-day precision (RSD) values were below 8.2 and 4.8% for ramipril, 10.4 and 12.3% for ramiprilat, and accuracy (RE) were within ±5.5 and ±3.2%, respectively at all QC levels. The method was utilized to support clinical pharmacokinetic studies in healthy volunteers following oral administration of ramipril tablets.     

LC–MS/MS Method for the Simultaneous Determination of Free Urinary Steroids

Cortisol homeostasis is implicated in hypertension and metabolic syndrome. Two enzymes modulate cortisol availability; 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) preferentially converts inactive cortisone to cortisol, whereas 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) converts cortisol to cortisone. In contrast, 5α and 5β reductases inactivate cortisol by conversion to its tetrahydrometabolites: tetrahydrocortisol, allo-tetrahydrocortisol and tetrahydrocortisone. A subtle local increase in cortisol can be detected by measuring 24-h urine metabolites, LC–MS/MS being the reference method. The 11β-HSD2 activity is assessed based on the cortisol/cortisone ratio, and the 11β-HSD1 activity on the (tetrahydrocortisol + allo-tetrahydrocortisol)/tetrahydrocortisone ratio. To better understand hypertension and/or metabolic syndrome pathogenesis a method for simultaneous determination of cortisol, cortisone, tetrahydrocortisol, allo-tetrahydrocortisol and tetrahydrocortisone was developed and validated in an LC coupled with the new detector AB Sciex QTrap^® 4500 tandem mass spectrometer. The steroids were extracted from 1 mL urine, using cortisol-D4 as internal standard. The quantification range was 0.1–120 ng/mL for cortisol and cortisone, and 1–120 ng/mL for tetrahydrometabolites, with >89 % recovery for all analytes. The coefficient of variation and accuracy was <10 %, and 85–105 %, respectively. Our LC–MS/MS method is accurate and reproducible in accordance with Food and Drug Administration guidelines, showing good sensitivity and recovery. This method allows the assessment of 11β-HSD2 and 11β-HSD1 activities in a single analytical run providing an innovative tool to explain etiology of misclassified essential hypertension and/or metabolic syndrome.     

Determination of Eleutherosides in Dietary Supplements by LC–MS/MS

A simple and specific method for the simultaneous determination of eleutherosides B and E in powdered rhizomes of Eleutherococcus senticosus extract and in solid and liquid dietary supplements was developed and validated. E. senticosus extracts, often mixed with other plants or herbal extracts, are widely used in food supplements because of the tonic and adaptogenic activities referred to the eleutherosides B and E. In this study, samples were analyzed by a liquid chromatography-electrospray tandem mass spectrometry (LC–ESI-MS/MS) method operated in single reaction monitoring (SRM). Validation was carried out in terms of limit of detection (LOD), limit of quantitation (LOQ), linearity, precision and trueness. LOD and LOQ values were fixed at 3 μg L^?1 and 10 μg L^?1, respectively, whereas linearity was established within 10–1,000 μg L^?1 range for both compounds. Good precision was obtained for both eleutherosides in terms of intra-day precision (RSD % lower than 4 %) and inter-day precision (RSD % lower than 6 %). Good percentage recoveries were obtained for both eleutherosides (91.5–103.6 %). Finally, the developed method was successfully applied to analyze a number of solid and liquid commercial dietary supplements containing E. senticosus extracts, also mixed with other herbal extracts.     

LC–MS/MS Method for Simultaneous Determination of Monoethanol- and Dimethylnitramine in Aqueous Soil Extracts

Monoethanol (MEA)- and dimethyl (DMA)-nitramines are by-products of amine-based post-combustion CO₂ capture (PCCC) processing, and are potentially carcinogenic. The compounds are challenging to measure, also with LC–tandem mass spectrometry (MS/MS), attributed to their high polarity and extreme proneness to matrix effects. In contrast to related methods, the MEA- and DMA-nitramines were simultaneously determined in aqueous soil extracts in less than 10 min using a 1 mm × 150 mm Atlantis^® T3 (3 µm) C18 column. A mobile phase of water/methanol (90/10, v/v) and 2 mM acetic acid allowed for electrospray ionization (ESI) of both analytes [in contrast to the need for both ESI and atmospheric pressure chemical ionization (APCI) in related methods]. Polarity switching electrospray was required for the simultaneous detection of the analytes, and concentration limits of detection (LODs) in the aqueous soil extracts were ≤5.0 µg L^?1 using an injection volume of 20 μL and no prior enrichment step. Matrix effects were compensated for using isotope-labelled internal standards, and satisfactory precision and linearity were obtained (within- and between-day precisions ≤19%, r ² ≥ 0.995 for concentrations up to 500.0 µg L^?1). To avoid signal decrease over time when measuring DMA-nitramine alone, the use of polarity switching was beneficial, in addition to frequent cleaning of the ion transfer capillary. The validated method can be used to determine nitramines in aqueous soil extracts, which is of importance as soil sorption is a determinant of the compounds’ environmental fate.     

Pressurized Liquid Extraction Coupled with LC–ESI–MS–MS for the Determination of Herbicides Chlormequat and Mepiquat in Flours

This paper describes a new method for the rapid extraction and unequivocal confirmation of herbicides chlormequat and mepiquat in wheat flours and various flours utilized in infant foods. The highly automated extraction procedure is based on accelerated solvent extraction, followed by liquid chromatography-tandem mass spectrometry as a confirmatory analysis. Typical recoveries from flours and baby food samples ranged from 83 to 99% at a fortification level of 10 ppb, corresponding to the maximum residue limits established by the European Union; while relative standard deviations (RSD) were less than 10% for all samples. The limit of detection (signal-to-noise ratio = 3) of the method for the considered phenols in baby food samples are less than 0.1 μg g^?1. Traces of the selected herbicides have been detected in about 50% of baby foods, bought from different Roman supermarkets and butcher shops, applying the described methodology.     

Application of Sol–Gel Based Poly(ethylene glycol)/Multiwalled Carbon Nanotubes Coated Fiber for SPME of Methyl tert-Butyl Ether in Environmental Water Samples

In this research, the sol–gel technology was applied for the preparation of solid-phase microextraction fibers for extracting of methyl tert-butyl ether (MTBE) from environmental water samples. For this purpose, two different polymers such as poly(ethylene glycol) (PEG) and combination of PEG and multiwall carbon nanotubes (MWCNTs) were prepared using sol–gel technology as coating procedure for the fibers. The pre-concentration process followed by GC–FID determination was used and the results evidenced that pre-concentration factor for PEG/CNTs fiber was approximately five times higher than PEG. Parameters affecting the extraction efficiency such as temperature, extraction time, stirring speed and salt effect for each fiber were investigated and optimized. On the optimal conditions, the linear range for MTBE with PEG and PEG/CNT fibers were 10–3,000 and 1–1,000 ng mL^?1 and the detection limits (S/N = 3) were 1.0 and 0.3 ng mL^?1, respectively. The sol–gel PEG/CNTs fiber has good performance and therefore relatively better figures of merit and experimental results such as thermal stability (up to 320 °C), average of life time (over 150 times) and repeatability (RSD < 4) in comparison to conventional PDMS/Carboxen fiber, which was already reported for determination of MTBE.     

Determination of Seven Odorants in Purified Water Among Worldwide Brands by HS-SPME Coupled to GC–MS

Musty and earthy odors dramatically influence the esthetic quality and consumer acceptability of drinking water. This study was conducted to obtain a sensitive method for simultaneous analysis of seven odors, including geosmin (GSM), 2-methylisoborneol (2-MIB), 2-isopropyl-3-methoxy pyrazine (IPMP), dimethyl trisulfide (DMTS), 2,4,6-trichloroanisole (2,4,6-TCA), β-cyclocitral, and β-ionone, in water by applying headspace solid phase micro-extraction coupled to gas chromatography with mass spectrometry. Moreover, the proposed method was applied to obtain preliminary understanding of the levels of these odorants in purified water among various brands in the world, and to try to find out the potential causes when the odorants appeared in purified water. The target compounds could be separated and analyzed effectively within 23 min, and the GSM and DMTS could be detected in all brands of chosen countries, while the IPMP, β-ionone and 2,4,6-TCA cannot be observed in the above brands.     

Determination of Amphotericin B in Human Cerebrospinal Fluid by LC–MS–MS

A simple, specific and sensitive column liquid chromatography–tandem mass spectrometry method has been developed for the determination of amphotericin B in human cerebrospinal fluid. Samples were prepared by dilution with methanol and quantitated by MS–MS detection in the positive mode. The determination was validated in the concentration range of 0.5–100 ng mL^?1 using 100 μL of human cerebrospinal fluid. The method was successfully used to support routine therapeutic drug monitoring.     

LC–MS Simultaneous Determination of Itopride Hydrochloride and Domperidone in Human Plasma

A rapid, simple, sensitive and specific liquid chromatography–tandem mass spectrometry method was developed and validated for simultaneous quantification of itopride hydrochloride and domperidone in human plasma. Both drugs were extracted by liquid–liquid extraction with ethyl acetate and saturated borax solution. The chromatographic separation was performed on a reversed-phase C18 column with a mobile phase of water–methanol (2:98, v/v) containing 0.5% formic acid. The protonated analyte was quantitated in positive ionization by multiple reaction monitoring with a mass spectrometer. The assay exhibited linearity over the concentration range of 3.33–500 ng mL^?1 for itopride hydrochloride and 3.33–100 ng mL^?1 for domperidone in human plasma. The precursor to product ion transitions of m/z 359.1–72.3 and 426.0–147.2 were used to measure itopride hydrochloride and domperidone respectively. The method was found suitable for the analysis of plasma samples collected during phase 1 pharmacokinetics study of itopride HCl 50 mg and domperidone 20 mg in 12 healthy volunteers after single oral doses of the combination drug.     

Simultaneous Determination of 42 Pesticides and Herbicides in Chicken Eggs by UHPLC–MS/MS and GC–MS Using a QuEChERS-Based Procedure

A quick, easy, cheap, rugged, effective, and safe (QuEChERS)-based method has been validated for the extraction of 42 pesticides and herbicides including organophosphorus pesticides (OPPs), carbamate pesticides (CBs), herbicides (HBs), organochlorine pesticides (OCPs), and synthetic pyrethroid pesticides (PYRs) from chicken eggs. The QuEChERS-based extraction procedure was followed by cleanup steps using C18 and primary secondary amine sorbents. The supernatant was analyzed by ultra-high performance liquid chromatography–tandem mass spectrometry (UHPLC–MS/MS) and gas chromatography–mass spectrometry (GC–MS). The OPPs, CBs, and HBs were quantified by UHPLC–MS/MS, while the OCPs and PYRs were detected by GC–MS. The limits of quantification ranged from 0.01 to 8.5 μg kg⁻¹, and the analyte recoveries were in the range of 64.9–123.2 %. Furthermore, the repeatabilities (intra-day and inter-day) were good, and linear matrix-matched calibration curves were obtained. Acetochlor was identified in concentrations ranging from 0.27 to 0.44 μg kg⁻¹ in four samples from 80 chicken eggs. The method was successfully demonstrated for the fast and reliable analysis of pesticides and herbicides in chicken egg samples.

     

LC Determination of Trace Amounts of Phenoxyacetic Acid Herbicides in Water after Dispersive Liquid–Liquid Microextraction

Dispersive liquid–liquid microextraction (DLLME) for extraction and preconcentration of phenoxyacetic acid herbicides in water samples is described. After adjusting the pH to 1.5, the sample was extracted in the presence of 10% w/v sodium chloride by injecting 1 mL acetone as disperser solvent containing 25 μL of chlorobenzene as extraction solvent. The effect of parameters, such as the nature and amount of extraction and disperser solvents, ionic strength of the sample, pH, temperature and extraction time were optimized. DLLME was followed by LC for the determination of 2,4-dichlorophenoxyacetic acid and 4-chloro-2-methyl phenoxyacetic acid. The method had good linearity and a wide linear dynamic range (0.5–750 μg L^?1) with a detection limit of 0.16 μg L^?1 for both the PAAs, making it suitable for their determination in water samples.