Rapid simultaneous determination of 14 sulfonamides in wastewater by liquid chromatography tandem mass spectrometry

This paper describes a rapid method for the determination of 14 kinds of sulfonamides (SAs) in wastewater using SPE, and LC-MS/MS with positive ESI (ESI(+)) and selected reaction monitoring (SRM) mode. The SPE was performed on an Oasis hydrophilic-lipophilic-balanced (HLB) cartridge. Chromatographic separation on a C18 column was achieved using a binary eluent containing methanol and water with 0.2% formic acid. Typical recoveries of the analytes ranged from 22.3 to 87.0% at a fortification level of 100 ng/L. The LODs in wastewater except sulfathiazole (3 ng/L) could be detected and quantified at levels as low as 1 ng/L. Finally, the method was applied to water from the municipal outlet and the aquaculture wastewater effluent. Sulfamethazine (SM(2)), sulfamethoxypyridazine (SMP), and sulfamethoxazole (SMZ) were most frequently found in wastewater in a concentration range between 1.2 and 31.7 ng/L.     

Development of a sensitive liquid chromatography/tandem mass spectrometry method for the determination of fenofibric acid in rat plasma

A rapid and sensitive LC‐MS/MS method for the quantification of fenofibric acid in rat plasma was developed and validated. Plasma samples were prepared by liquid–liquid extraction with a mixture of N‐hexane–dichloromethane–isopropanol (100:50:5, v/v/v). Isocratic chromatographic separation was performed on a reversed‐phase Discovery C₁₈ column (2.1 × 50 mm, 5 µm). The mobile phase was methanol–water–formic (75:25:0.25, v/v/v). Detection of fenofibric acid and the internal standard (IS) diclofenac acid was achieved by ESI MS/MS in the negative ion mode using m/z 317 → m/z 213 and m/z 294 → m/z 250 transitions, respectively. The method was linear from 0.005 to 1.250 µg/mL when 100 μL plasma was analyzed. The lower limit of quantification was 0.005 µg/mL. The intra‐ and inter‐day precision values were below 8.2%, and accuracy ranged from ?0.9 to 2.1% in all quality control samples. The recovery was 90.3–94.7% and 83.3% for fenofibric acid and IS, respectively. Total run time for each sample analysis was 2.5 min. The validated method was successfully applied to a pharmacokinetic study in six rats after oral administration of fenofibrate, the ester prodrug of fenofibric acid (equivalent to fenofibric acid 5 mg/kg). The method permits laboratory scientists with access to the appropriate instrumentation to perform rapid fenofibric acid determination. Copyright © 2011 John Wiley & Sons, Ltd.     

A rapid method with ultra‐high‐performance liquid chromatography–tandem mass spectrometry for simultaneous determination of five type B trichothecenes in traditional Chinese medicines

A speedy and selective ultra‐HPLC‐MS/MS method for simultaneous determination of deoxynivalenol (DON), 3‐acetyldeoxynivalenol (3‐ADON), 15‐ADON, nivalenol and fusarenon X in traditional Chinese medicines (TCMs) was developed. The method was based on one‐step sample cleanup using reliable homemade cleanup cartridges. A linear gradient mobile‐phase system, consisting of water containing 0.2% aqueous ammonia and acetonitrile/methanol (90:10, v/v) at a flow rate of 0.4 mL/min, and an Acquity UPLC HSS T3 column (100 mm×2.1 mm, 1.8 μm) were employed to obtain the best resolution of the target analytes. [¹³C₁₅]–DON was used as the internal standard to accomplish as accurate as possible quantitation. The established method was further validated by determining the linearity (R²≥0.9990), sensitivity (LOQ, 0.29–0.99 μg/kg), recovery (88.5–119.5%) and precision (RSD≤15.8%). It was shown to be a suitable method for simultaneous determination of DON, 3‐ADON, 15‐ADON, nivalenol and fusarenon X in various TCM matrices. The utility and practical impact of the method was demonstrated using different TCM samples.     

A sensitive method for determination of salvianolic acid A in rat plasma using liquid chromatography/tandem mass spectrometry

Salvianolic acid A (SAA), a major effective constituent of Salvia miltiorrhizas, is widely used in traditional Chinese medicine. A sensitive rapid analytical method was established and validated for SAA in rat plasma, which was further applied to assess the pharmacokinetics of SAA in rats receiving a single oral dose of SAA. The method used liquid chromatography tandem mass spectrometry in multiple reaction monitoring mode with chloramphenicol as the internal standard. A simple liquid-liquid extraction based on ethyl acetate was employed. The combination of a simple sample cleanup and short chromatographic run time (3 min) increased the throughput of the method substantially. The method was validated over the range 1.4-1000 ng/mL with a correlation coefficient >0.99. The lower limit of quantification was 1.4 ng/mL for SAA in plasma. Intra- and inter-day accuracies for SAA were 95-113 and 98-107%, and the inter-day precision was less than 12%. This method is more sensitive and faster than previous methods. After a single oral dose of 100 mg/kg of SAA, the mean peak plasma concentration (Cmax) of SAA was 318 ng/mL at 0.5 h, the area under the plasma concentration-time curve (AUC0-12 h) was 698 +/- 129 ng.h/mL, and the elimination half-life (T1/2) was 3.29 h.     

Rapid simultaneous determination of dexamethasone and betamethasone in milk by liquid chromatography tandem mass spectrometry with isotope dilution

A simple, sensitive and reliable analytical method for the rapid simultaneous determination of dexamethasone and betamethasone in milk by high performance liquid chromatography–negative electrospray ionization tandem mass spectrometry (HPLC–NESI-MS/MS) with isotope dilution was developed. Samples were directly purified through C₁₈ cartridge. Then the eluate was dried under nitrogen and residues were dissolved in mobile phase. Samples were analyzed by HPLC–MS/MS on a Hypercarb graphite column with a mixture of acetonitrile–water–formic acid as mobile phase. The samples were quantified using dexamethasone-D₄ as an internal standard. The procedure was validated according to the European Union regulation 2002/657/EC determining specificity, decision limit (CCα), detection capability (CCβ), trueness, precision, linearity and stability. The method is demonstrated to be suitable for the determination of dexamethasone and betamethasone in milk. The total time required for the analysis of one sample was about 35 min.     

A liquid chromatography/tandem mass spectrometry method for determination of aristolochic acid‐I in rat plasma

A sensitive, rapid and specific liquid chromatography–electrospray ionization–tandem mass spectrometry method was developed and validated for the determination of aristolochic acid‐I (AA‐I) in rat plasma. Finasteride was used as the internal standard (IS). The analyte was separated on a Zorbax Eclipse XDB‐C₁₈ column by isocratic elution with methanol‐10 mM ammonium acetate (75:25, v/v, pH = 7.3) at a flow rate of 0.25 mL/min, and analyzed by mass spectrometry in positive multiple reaction monitoring mode. The precursor‐to‐product ion transitions of m/z 359.0 → 298.2 and m/z 373.1 → 305.2 were used to detect AA‐I and IS, respectively. Good linearity was achieved over a range of 0.4–600 ng/mL. Intra‐ and inter‐day precisions measured as relative standard deviation were less than 13.5%, and accuracy ranged from 94.2 to 97.5%. The developed method was successfully applied in the pharmacokinetic study of AA‐I in rats. Copyright © 2009 John Wiley & Sons, Ltd.     

Rapid and sensitive method for simultaneous determination of six carcinogenic aromatic amines in mainstream cigarette smoke by liquid chromatography/electrospray ionization tandem mass spectrometry

Aromatic amines are one of the sources of carcinogenicity in cigarette and tobacco smoke. Accurate quantification of these chemicals is needed to assess public health risk. A new validated rapid, sensitive and analyte specific liquid chromatography/electrospray ionization tandem mass spectrometric (LC/MS/MS) method has been developed for the simultaneous determination of six aromatic amines in mainstream cigarette smoke using research reference cigarette 2R4F. Three popular Indian brand cigarettes were also analyzed using the same procedure. The limit of detection of this method ranged from 0.04 to 0.59 ng/cig using an injection volume of 7 μl. The identification of each amine was established by chromatographic retention times, analyte specific fragmentation pattern and relative peak area ratios of two product/precursor ion pairs. The method showed excellent reproducibility and was also rapid, selective and robust for aromatic amine determination from cigarette smoke.     

Quantitative determination of uridine in rabbit plasma and urine by liquid chromatography coupled to a tandem mass spectrometry

Recently a pyrimidine nucleoside, uridine, has been show to have a protective effect on cultured human corneal epithelial cells, and on dry eye animal model and patients. In this study, we introduce a sensitive liquid chromatography/tandem mass spectrometry method for the determination of uridine in rabbit plasma and urine. After protein precipitation with methanol including methaqualone (internal standard), the analyte was chromatographed on a reversed-phase column with a mobile phase of 0.1% formic acid aqueous solution and methanol (1:4, v/v). The accuracy and precision of the assay were in accordance with Food and Drug Administration regulations for the validation of bioanalytical methods. This method was used to measure the concentrations of uridine in plasma and urine after a single oral administration of 450 mg/kg uridine in rabbits.     

Simultaneous determination of zolazepam and tiletamine in dog plasma by liquid chromatography coupled to a tandem mass spectrometry

A mixture of tiletamine, a dissociative anesthetic, and zolazepam, a minor tranquilizer, has been widely used as an anesthetic or an immobilizing agent in a variety of animal species. However, interestingly, their pharmacokinetic behaviors have been published only in polar bears and pigs. In this study, we introduce a sensitive liquid chromatography/tandem mass spectrometry (LC/MS/MS) method for determining the two drugs in dog plasma. After simple protein precipitation with acetonitrile including midazolam (internal standard), the analytes were chromatographed on a reversed‐phase column with a mobile phase of 10 m m ammonium acetate aqueous solution and acetonitrile (1:4, v/v). The accuracy and precision of the assay were in accordance with FDA regulations for the validation of bioanalytical methods. This method was used to measure the concentrations of zolazepam and tiletamine in plasma after a single intramuscular 10 mg dose of each in beagle dogs. Copyright © 2012 John Wiley & Sons, Ltd.     

A sensitive and specific liquid chromatography/tandem mass spectrometry method for determination of echinacoside and its pharmacokinetic application in rats

A rapid and sensitive method based on liquid chromatography/tandem mass spectrometry (LC/MS/MS) for the determination of echinacoside in rat plasma was established and fully validated. A single step of liquid–liquid extraction with n‐butanol was utilized. Chromatographic separation of the analyte and the internal standard (IS), chlorogenic acid, from the sample matrix was performed using a Capcell‐MG C₁₈ analytical column (100 2.0 mm × 5 µm), with a gradient of acetonitrile and water containing 0.1% acetic acid as the mobile phase. Detection was performed on a triple quadrupole tandem mass spectrometer equipped with electrospray ionization source operated in negative ion selected reaction monitoring mode. The method was linear in the concentration range 10–2500 ng/mL. The deviations of both intra‐ and inter‐day precisions (RSD) were 7.1% and the assay accuracies were within 99.2–106.5%. Echinacoside proved to be stable during sample storage, preparation and analysis when an antioxidant solution was used. The method was successfully applied to a pharmacokinetic study in rats after an intragastric administration of echinacoside (100 mg/kg). With the lower limit of quantification at 10 ng/mL, this method proved to have sufficient selectivity, sensitivity and reproducibility for the pharmacokinetic study of echinacoside. Copyright © 2009 John Wiley & Sons, Ltd.     

A sensitive method for determination of furanodiene in rat plasma using liquid chromatography/tandem mass spectrometry and its application to a pharmacokinetic study

Furanodiene, a sesquiterpene component extracted from the essential oil of the rhizome of Curcuma wenyujin Y.H. Chen et C. Ling (Wen Ezhu), is widely used in traditional Chinese medicine. A sensitive analytical method was established and validated for furanodiene in rat plasma, which was further applied to assess the pharmacokinetics of furanodiene in rats receiving a single dose of furanodiene. Liquid chromatography tandem mass spectrometry (LC/MS/MS) in multiple reaction monitoring mode was used in the method and costundide was used as internal standard. A simple protein precipitation based on methanol was employed. The simple sample cleanup increased the throughput of the method substantially. The method was validated over the range of 1–1000 ng/mL with a correlation coefficient >0.99. The lower limit of quantification was 1 ng/mL for furanodiene in plasma. Intra‐ and inter‐day accuracies for furanodiene were 88–115 and 102–107%, and the inter‐day precision less than 14.4%. After a single oral dose of 10 mg/kg of furanodiene, the mean peak plasma concentration of furanodiene was 66.9 ± 23.4 ng/mL at 1 h, the area under the plasma concentration–time curve (AUC_{0–10 h}) was 220 ± 47.8 h ng/mL, and the elimination half‐life was 1.53 ± 0.06 h. After an intravenous adminstration of furanodiene at a dosage of 5 mg/kg, the area under the plasma concentration–time curve was 225 ± 76.1 h?ng/mL, and the elimination half‐life was 2.40 ± 1.18 h. Based on this result, the oral bioavailability of furanodiene in rats at 10 mg/kg is 49.0%. Copyright © 2011 John Wiley & Sons, Ltd.     

超高效液相色谱-串联质谱法同时测定聚合物食品包装材料中8种添加剂

建立了同时测定聚合物食品包装材料中8种常用添加剂Irgafos 168、Irganox 1010、Irganox 1076、丁基羟基茴香醚（BHA）、没食子酸丙酯（PG）、没食子酸十二酯（DG）、叔丁基对苯二酚（TBHQ）和苯三唑甲酚（UV-326）的超高效液相色谱-串联质谱方法。试样以二氯甲烷为溶剂进行超声提取;采用Waters BEH-C18柱（50 mm×2.1 mm,1.7 μm）分离,以0.05%甲酸水溶液和甲醇为流动相进行梯度洗脱;采用电喷雾离子源正、负离子切换模式和多反应监测模式进行检测。8种添加剂在相应的质量浓度范围内定量离子的峰面积与质量浓度均呈良好线性关系（相关系数R²均大于0.993）,回收率为63.9%~127.0%,相对标准偏差（RSD,n=6）≤15.8%,检出限（S/N=3）为0.13~5.50 μg/L,定量限（S/N=10）为0.45~17.50 μg/L。该方法简便快捷、灵敏度高,适合食品包装材料中常用添加剂的分析测定。     

Multi-residue confirmatory method for the determination of twelve coccidiostats in chicken liver using liquid chromatography tandem mass spectrometry

The confirmatory LC-MS/MS method for the determination of residues for twelve coccidiostats including ionophore antibiotics (lasalocid, maduramycin, monensin, narasin, salinomycin, semduramycin) and chemical coccidiostats (clazuril, decoquinate, diclazuril, halofuginone, nicarbazin and robenidine) in poultry liver has been developed. The sample preparation was based on extraction with acetonitrile, defatting with Alumina columns and clean-up on Oasis HLB spe. The separation of analytes was performed on PhenylHexyl column with a gradient of acetonitrile, methanol and the ammonium formate pH 4.0. For all analytes, at least 2 diagnostic fragmentation ions were monitored. The validation, performed according to the CD 2002/657/EC, proved the suitability of the method for the confirmatory analysis of the coccidiostats. For lasalocid, however, low reproducibility was observed and the proper quantification could not be performed with this method.     

Rapid and sensitive liquid chromatography tandem mass spectrometry method for the quantification of ambroxol in human plasma

A sensitive, specific and rapid high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was described and validated for the quantification of ambroxol in human plasma using enalaprilat as the internal standard (IS). Chromatographic separation was performed on a Lichrospher CN column with a mobile phase of methanol and water (containing 0.1% formic acid) (70:30, v/v). The total run time was 5.0 min for each sample. The analytes was detected by mass spectrometry with electrospray ionization source in positive selected reaction monitoring mode. The precursor-fragment ion reaction for ambroxol was m/z 378.9 --> 263.8, and for IS was m/z 349.0 --> 205.9. The linearity was established over the concentration range of 1.56-400.00 ng/mL. The inter-day and the intra-day precisions were all within 10%. A simple protein precipitation with methanol was adopted for sample preparation. The extraction recoveries of ambroxol and IS were higher than 90.80%. The validated method was successfully applied in pharmacokinetic study after oral administration of 90 mg ambroxol to 24 healthy volunteers.     

Development and validation of a liquid chromatography/tandem mass spectrometry method for the quantification of flucloxacillin and cloxacillin in microdialysis samples

In the present study we developed and validated a liquid chromatography/tandem mass spectrometry (LC‐MS/MS) assay for the determination of flucloxacillin in human plasma and microdialysis samples and cloxacillin in microdialysis samples, using oxacillin as the internal standard for the assay. The samples were separated on a UPLC BEH C₁₈,1.7 µm column (2.1 × 50 mm) and analyzed by a tandem–quadrupole mass spectrometer in multiple reaction monitoring mode using an electronspray ionization interface. For flucloxacillin the method was demonstrated to be accurate and precise in the linearity range of 1–30 mg/L in plasma and 0.05–5.0 mg/L for microdialysate with a regression coefficient (r) of 0.9986 and 0.9989 in plasma and microdialysate respectively. For cloxacillin it was accurate and precise in the range of 0.1–5.0 mg/L for microdialysate with a regression coefficient of 0.9972. The method presents a high sensitivity for flucloxacillin (lower limit of quantification of 1 mg/L for plasma and 0.05 mg/L for microdialysis samples) combined with a low within‐ and between‐day variation (<5.0% for flucloxacillin and cloxacillin in microdialysis samples and <6.5% for plasma samples of flucloxacillin). The validation experiments for the microdialysis probes showed a relative recovery of 85.5% for flucloxacillin at a flow rate of 1.0 μL/min. The results justify the use of this assay for clinical studies for measuring free unbound tissue concentrations of flucloxacillin in patients with a Staphylococcus aureus bacteremia. Copyright © 2014 John Wiley & Sons, Ltd.     

Simultaneous screening and determination of 18 illegal adulterants in herbal medicines and health foods for male sexual potency by ultra‐fast liquid chromatography‐electrospray ionization tandem mass spectrometry

An ultra‐fast liquid chromatography‐electrospray ionization tandem mass spectrometry method was developed and validated to simultaneously screen, confirm, and determine 18 illegal adulterants in herbal medicines and health foods for male sexual potency. The separation was achieved on a Shim‐Pack XR‐ODS II column (2.0 × 100 mm, 2.2 μm) with acetonitrile and aqueous solution (12 mmol/L ammonium formate, 0.01% acetic acid) as mobile phase at a flow rate of 0.4 mL/min with a gradient elution. The column temperature was maintained at 40°C and the run time was within 18 min. The 18 illegal adulterants were detected in electrospray ionization positive mode by multiple‐reaction monitoring. All the calibration curves showed good linearity with correlation coefficient (r) higher than 0.996 within the tested concentration ranges. The extraction recoveries and relative recoveries were in the range of 79.5–114% and 82.0–120%, respectively. The RSD of repeatability and intermediate precision was all less than 18% and the accuracy was in the range of 81.7–118%. The intra‐day and inter‐day stability was in the range of 86.8–110%. The validated method was successfully applied to screen, confirm, and determine 16 samples. Nine products were confirmed to contain illegal adulterants and the contents of adulterants were related to the therapeutic dosages.     

Development and validation of a liquid chromatography tandem mass spectrometry method for the measurement of urinary catecholamines in diagnosis of pheochromocytoma

The measurement of catecholamines in human body fluids is requested frequently for the differential diagnosis and monitoring of pheochromocytoma. The methods in most clinical laboratories focus on high‐performance liquid chromatography coupled with electrochemical detection, which suffers from high background noise, low sensitivity, and poor separation. We reported and developed a robust high‐throughput liquid chromatography tandem mass spectrometry method in routine clinical laboratories for the measurement of urinary catecholamines for diagnosis of pheochromocytoma. The method was validated for consistent linearity, good recovery (88–112%), excellent stability and low carryover. Intra‐ and inter‐assay precision values for catecholamines were all below 3.35 and 4.83% respectively. Dilution linearity was investigated with satisfactory linearly dependent coefficients (r > 0.9988). The reference intervals were obtained from 310 results derived from patients in which the diagnosis of pheochromocytoma was excluded. This method was successfully used in our laboratory. The clinical characteristics of patients have been explored with satisfactory sensitivity and specificity. Therefore, we have developed a reliable assay for the liquid chromatography tandem mass spectrometry measurement of catecholamines in a routine clinical laboratory. The assay requires a small volume of urine, and all analytes are measured simultaneously. The assay is rapid and reliable to be executed, offering the potential for routine clinical laboratories.     

4-Methylamino antipyrine determination in human plasma by high-performance liquid chromatography tandem mass spectrometry

In the present study, a simple and rapid method for metamizole metabolite 4-methylamino antipyrine (MAA) determination in human plasma was developed, validated and successfully applied to a clinical trial. Chromatographic separation was achieved in HILIC mode on a YMC-Pack SIL column (100 × 2.0 mm; S-5 μm, 30 nm), with a mobile phase consisting of acetonitrile, water and formic acid. Protein precipitation of a small plasma volume using acetonitrile was selected for sample preparation. The multiple reaction monitoring transitions in the positive ionization mode were m/z 218.2 → 56.2 for MAA and m/z 221.2 → 56.2 for MAA-d3 (IS, internal standard). Concentration levels of MAA calibration standards were in the range of 0.100–20 μg/ml. Metamizole conversion into MAA in both water and organic media was investigated, and the level of the conversion in commercially available injection solutions was estimated.     

Development and validation of a liquid chromatography method with electrospray ionization tandem mass spectrometry for the determination of brotizolam residues in beef and commercial whole milk

In this work, a liquid chromatography–tandem mass spectrometric detection technique was developed and validated for the determination of brotizolam residues in beef muscle and commercial whole milk. This procedure involves the extraction of the analyte from the samples via liquid–solid extraction, and caffeine was used as an internal standard. The analyte was successfully separated on an XTerra‐C₁₈ column, with a mobile phase composed of 0.01% formic acid in acetonitrile and 1 mm ammonium formate–0.01% formic acid in water. The one‐step extraction method evidenced good selectivity, precision (RSD = 9.87–26.47%), and the recovery of the extractable analyte was 92.61–115.98% in the matrices. The limits of quantification ranged between 0.4 and 0.5 µg/kg. The developed method is simple since it requires no additional cleanup procedures. Copyright © 2011 John Wiley & Sons, Ltd.     

Extraction and simultaneous determination of metoprolol and α-hydroxy metoprolol in latent fingerprints by liquid chromatography tandem mass spectrometry

Abstract

A simple extraction and sensitive simultaneous analysis method for metoprolol and its metabolite alpha-hydroxy metoprolol in latent fingerprint using liquid chromatography-mass spectrometry was developed. The extraction procedure was optimized as scrubbing using cotton swabs for 30 times followed by ultrasonic assistance in 30?°C methanol for 5?min with power of 2000 W. Drug analysis was performed using the mixture of methanol and 0.1% formic acid solution (pH 3.5, 30:70, v/v) as the mobile phase under positive electrospray ionization condition. The linear range obtained was 1.0–500.0?ng/mL for MET, and α-MET, and the limit of detection and the limit of quantification were 0.3?ng/cotton swab and 1.0?ng/cotton swab, respectively. The method showed very slight matrix effect and good recovery to the analytes in the fingermarks. Evaluation of extraction substrates and developing methods showed that the method developed is best used for impermeable substrates and that the commercially development powders have very slight influence on the qualitative detection of metoprolol in fingermarks. Finally, the drug users distinguishing test proved that the method developed for pharmaceuticals could be applied in the forensic analysis for circling out the pool of suspects in the criminal investigation based on their drug use history.