Quantification of pramipexole in human plasma by liquid chromatography tandem mass spectrometry using tamsulosin as internal standard

A high-performance liquid chromatography/electrospray ionization tandem mass spectrometry method was developed and validated for the quantification of pramipexole in human plasma. Following liquid-liquid extraction, the analytes were separated using an isocratic mobile phase on a reverse-phase column and analyzed by MS/MS in the multiple reaction monitoring mode using the respective [M + H](+) ions, m/z 212/152 for pramipexole and m/z 409/228 for the IS. The method exhibited a linear dynamic range of 200-8000 pg/mL for pramipexole in human plasma. The lower limit of quantification was 200 pg/mL with a relative standard deviation of less than 8%. Acceptable precision and accuracy were obtained for concentrations over the standard curve range. A run time of 3.5 min for each sample made it possible to analyze more than 200 human plasma samples per day. The validated method has been successfully used to analyze human plasma samples for application in pharmacokinetic, bioavailability or bioequivalence studies.     

Determination of a novel paclitaxel derivative (NPD‐103) in human plasma by ultra‐performance liquid chromatography–tandem mass spectrometry

A sensitive and specific ultra‐performance liquid chromatography–tandem mass spectrometry (UPLC‐MS‐MS) method for quantification of a newly developed anticancer agent NPD‐103 has been established. An aliquot of human plasma sample (200 µL) was spiked with ¹³C‐labeled paclitaxel (internal standard) and extracted with 1.3 mL of tert‐butyl methyl ether. NPD‐103 was quantitated on a C₁₈ column with methanol–0.1% formic acid (75:25, v/v) as mobile phase using UPLC‐MS‐MS operating in positive electrospray ionization mode with a total run time of 3.0 min. For NPD‐103 at the concentrations of 1.0, 5.0 and 10.0 µg/mL in human plasma, the absolute extraction recoveries were 95.58, 102.43 and 97.77%, respectively. The linear quantification range of the method was 0.1–20.0 µg/mL in human plasma with linear correlation coefficients greater than 0.999. The intra‐ and inter‐day accuracy for NPD‐103 at 1.0, 5.0 and 10.0 µg/mL levels in human plasma fell into the ranges of 95.29–100.00% and 91.04–94.21%, and the intra‐ and inter‐day precisions were in the ranges of 8.96–11.79% and 7.25–10.63%, respectively. This assay is applied to determination of half‐life of NPD‐103 in human plasma. Copyright © 2008 John Wiley & Sons, Ltd.     

Quantification of asenapine and three metabolites in human plasma using liquid chromatography-tandem mass spectrometry with automated solid-phase extraction: application to a phase I clinical trial with asenapine in healthy male subjects

The development and validation of methods for determining concentrations of the antipsychotic drug asenapine (ASE) and three of its metabolites [N-desmethylasenapine (DMA), asenapine-N(+) -glucuronide (ASG) and 11-O-sulfate-asenapine (OSA)] in human plasma using LC-MS/MS with automated solid-phase extraction is described. The three assessment methods in human plasma were found to be acceptable for quantification in the ranges 0.0250-20.0 ng/mL (ASE), 0.0500-20.0 ng/mL (DMA and OSA) and 0.250-50.0 ng/mL (ASG).     

Simultaneous determination of mifepristone and monodemethyl-mifepristone in human plasma by liquid chromatography-tandem mass spectrometry method using levonorgestrel as an internal standard: application to a pharmacokinetic study

A rapid and sensitive liquid chromatography/tandem mass spectrometry (LC-MS/MS) method was developed and validated to simultaneously determine mifepristone and monodemethyl-mifepristone in human plasma using levonorgestrel as the internal standard (IS). After solid-phase extraction of the plasma samples, mifepristone, monodemethyl-mifepristone and the IS were subjected to LC-MS/MS analysis using electro-spray ionization (ESI) in the multiple reaction monitoring (MRM) mode. Chromatographic separation was performed on an XTERRA MS C(18) column (150 x 2.1 mm i.d., 5 microm). The method had a chromatographic run time of 4.5 min and linear calibration curves over the concentration ranges of 5-2000 ng/mL for mifepristone and monodemethyl-mifepristone. The recoveries of the method were found to be 94.5-103.7% for mifepristone and 70.7-77.3% for monodemethyl-mifepristone. The method had a lower limit of quantification (LLOQ) of 5.0 ng/mL and a lower limit of detection (LOD) of 1.0 ng/mL for both mifepristone and monodemethyl-mifepristone. The intra- and inter-batch precision was less than 15% for all quality control samples at concentrations of 10, 100 and 1000 ng/mL. These results indicate that the method was efficient with a short run time (4.5 min) and acceptable accuracy, precision and sensitivity. The validated LC-MS/MS method was successfully used in a pharmacokinetic study in healthy female volunteers after oral administration of 25 mg mifepristone tablet.     

Determination of levonorgestrel in human plasma by liquid chromatography-tandem mass spectrometry method: application to a bioequivalence study of two formulations in healthy volunteers

A rapid and sensitive liquid chromatography-tandem mass spectrometry (LC/MS/MS) method to determine levonorgestrel in human plasma was developed and fully validated. After hexane-ethyl acetate (70:30, v/v) induced extraction from the plasma samples, levonorgestrel was subjected to LC/MS/MS analysis using electro-spray ionization. The MS system was operated in the selected reaction monitoring mode. Chromatographic separation was performed on a Hypersil BDS C18 column (i.d. 2.1x50 mm, particle size 3 microm). The method had a chromatographic running time of 2.0 min and linear calibration curves over the concentration ranges of 0.25-90 ng/mL for levonorgestrel. The lower limit of quantification of the method was 0.25 ng/mL for levonorgestrel. The intra- and inter-batch precision was 3.7-10.2 and 5.1-12.9%, respectively, for all quality control samples at concentrations of 0.5, 6.0 and 45.0 ng/mL. These results indicate that the method was efficient with a simple preparation procedure and a very short running time (2.0 min) for levonorgestrel compared with those methods reported in the literature and had high selectivity, acceptable accuracy, precision and sensitivity. The validated LC/MS/MS method was successfully used for a bioequivalence study of two tablet formulations of levonorgestrel in healthy volunteers.     

Sensitive liquid chromatography tandem mass spectrometry method for the quantification of Quetiapine in plasma

A sensitive high-performance liquid chromatography-tandem mass spectrometry method was developed and validated for the quantification of quetiapine in rat plasma. Following liquid-liquid extraction, the analyte was separated using a gradient mobile phase on a reverse-phase column and analyzed by MS/MS in the multiple reaction monitoring mode using the respective [M + H]+ ions, m/z 384 to m/z 221 for quetiapine and m/z 327 to m/z 270 for the internal standard. The assay exhibited a linear dynamic range of 0.25-500 ng/mL for quetiapine in rat plasma. The lower limit of quantification was 0.25 ng/mL with a relative standard deviation of less than 7%. Acceptable precision and accuracy were obtained for concentrations over the standard curve range. The validated method was successfully used to analyze rat plasma samples for application in pre-clinical pharmacokinetic studies. This method in rodent plasma could be adapted for quetiapine assay in human plasma.     

超高效液相色谱-串联质谱法测定人血浆中苯海索

建立了灵敏、高通量的超高效液相色谱-串联质谱（UPLC-MS/MS）定量测定人血浆中苯海索的方法,用于盐酸苯海索片生物等效性研究,并确证食物对苯海索体内药代动力学行为的影响。以甲醇为沉淀剂进行蛋白质沉淀,苯海索-d11为内标,采用Waters Acquity UPLC BEH C8色谱柱（50 mm×2.1mm,1.7 μm）,以0.1%（v/v）甲酸水溶液（含5 mmol/L醋酸铵）和乙腈-水（95：5,v/v）为流动相进行梯度洗脱;采用电喷雾电离（ESI）源,在正离子模式下进行多反应监测（MRM）扫描。苯海索在0.1~40 ng/mL范围内线性关系良好。应用该方法测定中国健康受试者空腹及餐后单次口服2 mg盐酸苯海索片后的血药浓度,结果显示最大血药浓度（C_max）、血药浓度-时间曲线下面积（AUC_0-t、AUC_0-∞）的90%置信区间均在80.0%~125.0%范围内,表明两种制剂在空腹和餐后均生物等效。     

Liquid chromatography tandem mass spectrometry method for the quantification of rimonabant, a CB1 receptor antagonist, in human plasma

A sensitive high-performance liquid chromatography-tandem mass spectrometry method was developed and validated for the quantification of rimonabant in human plasma. Following liquid-liquid extraction, the analytes were separated using an isocratic mobile phase on a reverse-phase column and analyzed by MS/MS in the multiple reaction monitoring mode using the respective (M+H)+ ions, m/z 463-363 for rimonabant and m/z 408-235 for the internal standard. The assay exhibited a linear dynamic range of 0.1-100 ng/mL for rimonabant in human plasma. The lower limit of quantification was 0.1 ng/mL with a relative standard deviation of less than 6%. With dilution integrity up to 10-fold, the upper limit of quantification was extendable up to 1000 ng/mL. Acceptable precision and accuracy were obtained for concentrations over the standard curve range. A run time of 2.0 min for each sample made it possible to analyze more than 250 human plasma samples per day. The validated method was successfully used to analyze human plasma samples for application in pharmacokinetic studies.     

Determination of cyantraniliprole and its major metabolite residues in vegetable and soil using ultra-performance liquid chromatography/tandem mass spectrometry

A rapid, highly sensitive and selective method was developed for the determination of the cyantraniliprole and its major metabolite J9Z38 in cucumber, tomato and soil by ultra‐performance liquid chromatography–tandem mass spectrometry (UPLC‐MS/MS). Target compounds were extracted with acetonitrile and an aliquot cleaned with primary and secondary amine. Two pairs of precursor product ion transitions for cyantraniliprole and J9Z38 were measured and evaluated. Average recoveries for cucumber, tomato and soil at three levels (10, 50 and 100 µg/kg) ranged from 74.7 to 96.2% with intra‐day relative standard deviation (RSD) of 2.6–15.1% and inter‐day RSD of 3.4–13.3%. The limit of quantitation for cyantraniliprole and J9Z38 were determined to be 5 and 10 µg/kg in samples (cucumber, tomato and soil), respectively. This method was used to determine the cyantraniliprole and J9Z38 residues in real cucumber, tomato and soil samples for studies on their dissipation. The trial results showed that the half‐lives of cyantraniliprole obtained after treatments were 2.2, 2.8 and 9.5 days in cucumber, tomato and soil in Zhejiang, respectively, and that the average levels of cyantraniliprole and J9Z38 residues in cucumber and tomato were all <0.01 mg/kg with the interval of 10 days after treatment. Copyright © 2011 John Wiley & Sons, Ltd.     

Liquid chromatography tandem mass spectrometry method for the quantification of clonidine with LLOQ of 10 pg/mL in human plasma

A sensitive high-performance liquid chromatography-positive ion electrospray tandem mass spectrometry method was developed and validated for the quantification of clonidine in human plasma. Following liquid-liquid extraction, the analytes were separated using an isocratic mobile phase on a reverse-phase column and analyzed by MS/MS in the multiple reaction monitoring mode using the respective [M + H](+) ions, m/z 230 to 44 for clonidine and m/z 254 to 44 for the internal standard. The assay exhibited a linear dynamic range of 10-2000 pg/mL for clonidine in human plasma. The lower limit of quantification was 10 pg/mL with a relative standard deviation of less than 6.8%. Acceptable precision and accuracy were obtained for concentrations over the standard curve range. A run time of 2.5 min for each sample made it possible to analyze more than 250 human plasma samples per day. The validated method was successfully used to analyze human plasma samples for application in pharmacokinetic studies. Copyright (c) 2008 John Wiley & Sons, Ltd.     

超高效液相色谱-串联质谱法测定人血浆中盐酸氨溴索及其制剂的生物等效性评价

采用超高效液相色谱-串联质谱（UHPLC-MS/MS）技术,建立了快速、简单、灵敏的测定人血浆中盐酸氨溴索含量的方法,并用于盐酸氨溴索人体生物等效性预试验研究。取50 μL血浆样品,采用蛋白沉淀法处理,以盐酸氨溴索-d5为内标。采用Waters XBridge BEH C18色谱柱（50 mm×2.1 mm,2.5 μm）,以0.1%（v/v）甲酸水-含0.1%（v/v）甲酸的甲醇为流动相,在0.4 mL/min流速下进行梯度洗脱。采用电喷雾电离（ESI）源以正离子模式进行MRM检测。结果显示,盐酸氨溴索在2~400 ng/mL范围内线性关系良好,相关系数（r）为0.998,准确度为97.1%~108.7%,精密度为1.0%~5.6%。将该方法用于6名健康受试者口服盐酸氨溴索受试制剂和参比制剂30 mg后血药浓度的测定,结果显示二者相对生物利用度为（102.3±14.8）%,血药浓度-时间曲线下面积（AUC_0-t、AUC_0-∞）和最大血药浓度（C_max）的90%置信区间均在80.0%~125.0%范围内,两种制剂生物等效。     

Determination of bromate in drinking water by ultraperformance liquid chromatography-tandem mass spectrometry

Bromate is a byproduct formed as a result of disinfection of bromide-containing source water with ozone or hypochlorite. The International Agency for Research on Cancer has recognized bromate as a possible human carcinogen, thus it is essential to determine in drinking water. Present work highlights a development of sensitive and fast analytical method for bromate determination in drinking water by using ultraperformance liquid chromatography-tandem mass spectrometry. The quality parameters of the developed method were established, obtaining very low limit of detection (0.01 ng/mL), repeatability and reproducibility have been found to be less than 3% in terms of relative standard deviation when analyzing a bromate standard at 0.05 μg/mL with 0.4 min analysis time. Developed method was applied for the analysis of metropolitan and bottled water from Saudi Arabia; 22 samples have been analyzed. Bromate was detected in the metropolitan water samples (from desalinization source) at concentrations ranging between 3.43 and 75.04 ng/mL and in the bottled water samples at concentrations ranging between 2.07 and 21.90 ng/mL. Moreover, in comparison to established analytical methods such as liquid chromatography-tandem mass spectrometry, the proposed method was found to be very sensitive, selective and rapid for the routine analysis of bromate at low level in drinking water.     

Simultaneous quantification of atenolol and chlorthalidone in human plasma by ultra‐performance liquid chromatography–tandem mass spectrometry

A simple, sensitive and reproducible ultra‐performance liquid chromatography–tandem mass spectrometry method has been developed for the simultaneous determination of atenolol, a β‐adrenergic receptor‐blocker and chlorthalidone, a monosulfonamyl diuretic in human plasma, using atenolol‐d7 and chlorthalidone‐d4 as the internal standards (ISs). Following solid‐phase extraction on Phenomenex Strata‐X cartridges using 100 μL human plasma sample, the analytes and ISs were separated on an Acquity UPLC BEH C₁₈ (50 mm × 2.1 mm, 1.7 µm) column using a mobile phase consisting of 0.1% formic acid–acetonitrile (25:75, v/v). A tandem mass spectrometer equipped with electrospray ionization was used as a detector in the positive ionization mode for both analytes. The linear concentration range was established as 0.50–500 ng/mL for atenolol and 0.25–150 ng/mL for chlorthalidone. Extraction recoveries were within 95–103% and ion suppression/enhancement, expressed as IS‐normalized matrix factors, ranged from 0.95 to 1.06 for both the analytes. Intra‐batch and inter‐batch precision (CV) and accuracy values were 2.37–5.91 and 96.1–103.2%, respectively. Stability of analytes in plasma was evaluated under different conditions, such as bench‐top, freeze–thaw, dry and wet extract and long‐term. The developed method was superior to the existing methods for the simultaneous determination of atenolol and chlorthalidone in human plasma with respect to the sensitivity, chromatographic analysis time and plasma volume for processing. Further, it was successfully applied to support a bioequivalence study of 50 mg atenolol + 12.5 mg chlorthalidone in 28 healthy Indian subjects. Copyright © 2015 John Wiley & Sons, Ltd.     

Rapid and simple liquid chromatography tandem mass spectrometry method for the quantification of zidovudine in rat plasma

A high-performance liquid chromatography/electrospray ionization tandem mass spectrometry method was developed and validated for the quantification of zidovudine in rat plasma. Following solid-phase extraction, the analytes were separated using an isocratic mobile phase on a reverse phase column and analyzed by MS/MS in the multiple reaction monitoring mode using the respective [M+H]+ ions, m/z 268/127 for zidovudine and m/z 230/112 for the internal standard. The method exhibited a linear dynamic range of 5-500 ng/mL for zidovudine in rat plasma. The lower limit of quantification was 5 ng/mL with a relative standard deviation of less than 8%. Acceptable precision and accuracy were obtained for concentrations over the standard curve range. A run time of 1.5 min for each sample made it possible to analyze more than 400 plasma samples per day. The validated method was applied for pharmacokinetic studies of the novel drug delivery systems of zidovudine in rats.     

Determination of teniposide in rat plasma by ultra performance liquid chromatography electrospray ionization tandem mass spectrometry after intravenous administration

A novel, specific and rapid ultra performance liquid chromatography electrospray ionization tandem mass spectrometry method has been developed and validated for determination of teniposide in rat plasma. A one‐step liquid–liquid extraction method was used and the separation was carried out on an Acquity UPLC^TM BEH C₁₈ column with gradient elution using a mobile phase composed of acetonitrile and water (containing 0.1% formic acid) at a flow rate of 0.20 mL/min. A triple quadrupole tandem mass spectrometer in multiple‐reaction monitoring mode via an electrospray ionization interface was used for the detection of teniposide. The detection was complete within 3.0 min. A linear calibration curve was obtained over the concentration range 10–10,000 ng/mL for teniposide, with a lower limit of quantification of 10 ng/mL. The intra‐day precision and inter‐day precision (relative standard deviation) were less than 10.23 and 13.09%, respectively. The developed method was applied for the first time to the pharmacokinetic study of teniposide in rats following a single intravenous administration of 4.5 mg/kg teniposide. Copyright © 2009 John Wiley & Sons, Ltd.     

Simultaneous determination of three bufadienolides in rat plasma after intravenous administration of bufadienolides extract by ultra performance liquid chromatography electrospray ionization tandem mass spectrometry

A novel, rapid and specific ultra performance liquid chromatography electrospray ionization tandem mass spectrometry (UPLC-ESI-MS/MS) method has been developed for simultaneous determination and pharmacokinetic studies of three bufadienolides (bufalin, cinobufagin and resibufogenin) in rat plasma. The analytes, bufalin, cinobufagin, resibufogenin and the internal standard, diphenhydramine were extracted from rat plasma samples by a one-step liquid–liquid extraction and separated on an ACQUITY UPLC™ BEH C₁₈ column with gradient elution using a mobile phase composed of acetonitrile and water (containing 0.1% formic acid) at a flow rate of 0.20 mL min⁻¹. Detection was carried out on a triple-quadrupole tandem mass spectrometer in the multiple reaction monitoring (MRM) mode via an electrospray ionization (ESI) interface. The three bufadienolides could be simultaneously determined within 3.0 min. Linear calibration curves were obtained over the concentration ranges of 1.0–200 ng mL⁻¹ for all the analytes. The intra- and inter-day precisions (relative standard deviation (R.S.D.)) were less than 11.35 and 10.87%, respectively. The developed method was applied for the first time to the pharmacokinetic studies of bufadienolides in rats following a single intravenous administration of 2.10 mg kg⁻¹ bufadienolides.     

Quantification of granisetron in human plasma by liquid chromatography coupled to electrospray tandem mass spectrometry

A simple, sensitive and rapid high-performance liquid chromatography/electrospray ionization tandem mass spectrometry method was developed and validated for the assay of granisetron in human plasma. Following liquid-liquid extraction, the analytes were separated using an isocratic mobile phase on a reversed-phase C18 column and analyzed by MS in the multiple reaction monitoring mode using the respective [M+H]+ ions, m/z 313/138 for granisetron and m/z 409/228 for the IS. The assay exhibited a linear dynamic range of 0.1-20 ng/mL for granisetron in human plasma. The lower limit of quantification was 100 pg/mL with a relative standard deviation of less than 5%. Acceptable precision and accuracy were obtained for concentrations over the standard curve range. A run time of 2.0 min for each sample made it possible to analyze more than 400 human plasma samples per day. The validated method has been successfully used to analyze human plasma samples for application in pharmacokinetic, bioavailability or bioequivalence studies.     

QuEChERS-超高效液相色谱-串联质谱法检测羊肉中8种抗真菌药

建立了QuEChERS-超高效液相色谱-串联质谱（UPLC-MS/MS）检测羊肉中8种抗真菌药的方法。羊肉样品用含2.0%（体积分数）甲酸的乙腈溶液提取后,采用QuEChERS方法净化。采用Atiantis^® T3色谱柱（100 mm×2.1 mm,3 μm）进行分离,以乙腈-0.1%（v/v）甲酸水溶液为流动相进行梯度洗脱,在电喷雾电离源、正离子模式（ESI⁺）和多反应监测模式（MRM）下进行定性定量分析。实验比较了不同提取溶剂的提取效果,并优化了色谱和质谱的分析条件。结果表明,8种抗真菌药物在0.2~50 μg/L范围内线性关系良好,相关系数（R²）均>0.99;检出限（LOD）为0.3~3.0 μg/kg,定量限（LOQ）为1.0~10.0 μg/kg。8种抗真菌药在低、中、高3个水平下的平均加标回收率为70.3%~118.4%,相对标准偏差（RSD）为0.4%~4.3%（n=6）。该方法灵敏高效,回收率优良,重复性好,适用于羊肉样品抗真菌药物的有效检测。     

Determination of caudatin-2,6-dideoxy-3-O-methy-beta-d-cymaropyranoside in rat plasma using liquid chromatography-tandem mass spectrometry

A selective, sensitive and rapid liquid chromatography-tandem mass spectrometry method has been developed for the determination of caudatin-2,6-dideoxy-3-O-methy-beta-d-cymaropyranoside (CDMC) in rat plasma. This method involves a plasma clean-up step using liquid-liquid extraction, followed by LC separation and positive electrospray ionization mass spectrometry detection (LC/ESI-MS/MS). Chromatographic separation of the analytes was achieved using a C(18) column with a mobile phase of acetonitrile and water (70:30, v/v) at a flow rate of 1.0 mL/min. Low energy collision tandem mass spectrometric analysis (CID-MS/MS) using the multiple reaction monitoring (MRM) mode was used for analyte quantification. For the MRM analysis of CDMC, the following transition at m/z 658.4 --> 529.6 derived from the protonated molecule [M + Na](+). A calibration curve was linear in the 5-500 ng/mL range for CDMC, and the limit of detection was 5 ng/mL. The inter- and intra-day precisions (RSD) were 相似文献   

Comparison of enzyme-linked immunosorbent assay with liquid chromatography-tandem mass spectrometry for the determination of diethylstilbesterol residues in chicken and liver tissues

A competitive enzyme-linked immunosorbent assay (ELISA) was developed for the quantitative detection of the diethylstilbesterol (DES). Polyclonal rabbit antisera, raised against protein conjugate diethylstilbesterol-mono-caroxyl-propyl-ethyl-bovine-serum-albumin (DES-MCPE-BSA), were utilized in immobilized antibody-based and competitive immunoassays. Assay conditions, including concentrations of antisera and horseradish peroxidase, (HRP)-DES, were optimized. The effects of incubation time, surfactant concentration, ionic strength and pH of the medium were also investigated. The typical calibration curve gave an average IC(50) value of 2.4 ng/mL, calibration range from 0.2 to 30.5 ng/mL and a detection limit of 0.07 ng/mL. The specificity of the assay was tested against DES structurally related compounds, and the assay proved highly selective for DES. Assay performance was validated using spiked chicken meat and liver tissue samples. Moreover, it was compared with liquid chromatography-tandem mass spectrometry. The ion pair for quantification of DES was m/z 267.4/251.4, and the linear equation of DES was y = 0.1033x + 0.0126 (r = 0.9960). The two analytical methods can be applied to monitor DES and other steroid residues in foods.