LC-ESI-MS/MS快速测定人血浆中匹伐他汀浓度

Rapid Determination of Pitavastatin in Plasma by LC-ESI-MS/MS

关键词:  匹伐他汀  血药浓度  高效液相色谱串联质谱检测法

摘要:

目的 建立一种快速灵敏测定人体血浆中匹伐他汀浓度的高效液相色谱串联质谱检测方法。方法 以Agilent C18柱(4.6 mm×150 mm，3.5 μm)为色谱柱，流动相为甲醇-0.005 mol·L^-1甲酸铵水溶液-乙腈-1%甲酸水溶液(7.5∶2.5∶70∶20)；流速：0.5 mL·min^-1，柱温：40 ℃。采用选择反应监测(SRM)对匹伐他汀(m/z 422.2→290.2)和内标瑞舒伐他汀(m/z 482.2→258.2)进行测定。结果 匹伐他汀高(80 μg·L^-1)、中(50 μg·L^-1)、低(0.25 μg·L^-1)3个浓度的平均回收率RSD均小于15%；线性范围为：0.1~100 μg·L^-1，回归方程为Y=1.222 6X-1.056 1×10^-4，r=0.996 0。结论 该方法灵敏、准确、简单、快速，可用于匹伐他汀临床血药浓度监测和药动学研究。

Abstract:

OBJECTIVE To set up a rapid and sensitive LC-ESI-MS/MS method for the determination of pitavastatin in plasma. METHODS Pitavastatin was extracted with ethyl acetate-dichloromethane. The residues were analyzed with a LC-MS/MS system (Agilent Eclipse Plus C₁₈ column, 4.6 mm×150 mm, 3.5 µm) with the mobile phase of methanol-0.005 mol·L^-1 ammonium formate aqueous solution-acetonitrile-1% formic acid(7.5∶2.5∶70∶20), with a flow rate of 0.5 mL·min^-1, temperature: 40 ℃. Selected reaction monitoring (SRM) using the precursor to production combinations of m/z 422.2→290.2 and m/z 482.2→258.2 was performed to detect pitavastatin and the internal standard, respectively. RESULTS The RSDs of average recovery of different concentration of pitavastatin(80, 50, 0.25 μg·L^-1) were less than 15%. The calibration curves for pitavastatin had good linearity over the range of 0.1-100 μg·L^-1, r=0.996 0. CONCLUSION The method provides a sensitive, accurate, precise and reliable analytical procedure for clinical monitoring of pitavastatin plasma and its phamacokinetic studies.