目的 建立LC-MS/MS同时测定大鼠血浆中氯维地平和其主要代谢产物H152/81的浓度。方法 大鼠血浆样品用液液萃取后,以尼莫地平为内标,选用ZORBAX SB C18(2.1 mm×100 mm, 3.5 μm)色谱柱,以乙腈-0.1%甲酸为流动相梯度洗脱,梯度流速恒定为0.3 mL·min-1,柱温为30 ℃,进样量10 μL,总分析时间为3.5 min,采用电喷雾离子化源,正离子方式,多反应监测(MRM)扫描方式进行监测。结果 血浆中氯维地平和代谢产物H152/81的线性范围为1.0~200 μg·L-1 (r＞0.99),定量下限为1.0 μg·L-1;平均回收率95.2%~109.8%;日内、日间RSD均小于15%;提取回收率在71.3%~82.6%。结论 该方法快速、灵敏、准确,专属性强,重复性好,适用于大鼠血浆中同时测定氯维地平及其代谢产物浓度。
Abstract
OBJECTIVE To develop an LC-MS/MS method for simultaneous determination of clevidipine and its major metabolite H152/81 concentration in rat plasma. METHODS The plasma samples were processed with liquid-liquid extraction, with nimodipin as an internal standard. The separation was achieved on ZORBAX SB C18 column (2.1 mm×100 mm, 3.5 μm) and eluted with linear gradient using acetonitrile and 0.1% formic acid at the flow rate of 0.3 mL·min-1,the injection volume was 10 μL and the column temperature was maitained at 30 ℃. The total time of the analysis was 3.5 min. Detection of the analytes were achieved using positive ion electrospray ionization(ESI) in the multiple reaction monitoring (MRM) mode. RESULTS The linear calibration curve of clevidipine and its major metabolite H152/81were obtained concentration range of 1.0-200 μg·L-1(r＞0.99), with the lower limit of quantitation(LLOQ) of 1.0 μg·L-1.The average recovery was between 92.5%-109.8%, Intra-day and inter-day relative standard deviations were both below 15%. The recoveries of low, middle and high concentrations were 71.3%-82.6%, respectively. CONCLUSION The established method is rapid, sensitive, accurate, specific and reliable, and suitable for simultaneous determination of clevidipine and its major metabolite H152/81 in rat plasma.
关键词
氯维地平 /
代谢产物 /
液质联用法 /
血药浓度 /
药动学
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Key words
clevidipine /
metabolite /
LC-MS/MS /
plasma drug concentration /
pharmacokinetics
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中图分类号：
R969.1
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参考文献
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[7] HOU Y, LI H, HE X, et al. Simultaneous determination of clevidipine and its primary metabolite in dog plasma by liquid chromatography-tandem mass spectrometry: Application to pharmacokinetic study.J Pharm Biomed Anal, 2014, 100(11):294-299.
[8] NORDLANDER M, SJOQUIST P O, ERICSSON H,et al. Pharmacodynamic, pharmacokinetic and clinical effects ofclevidipine, an ultrashort-acting calciumantagonist for rapid blood pressure control.Cardiovasc Drug Rev, 2004, 22(3):227-250.
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脚注
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基金
国家科技重大专项项目-老年病新药临床技术平台资助项目(2013ZX09303005)
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