LC-MS测定人血浆中匹伐他汀浓度及其应用

Determination of the Concentration of Pitavastatin in Human Plasma by LC-MS and Subsequent Application to a Clinical Study

关键词:  匹伐他汀  液相色谱-质谱联用  血药浓度

Key words:  pitavastatin  LC-MS  plasma drug concentration

摘要:

目的 建立LC-MS测定人血浆中匹伐他汀的浓度。方法 采用Shim-pack C₁₈色谱柱，流动相A为甲醇, 流动相B为含0.025% 氨水和0.05 mmol·L^-1醋酸铵的水溶液，采用梯度洗脱方式。质谱检测方式：SIM。以瑞舒伐他汀为内标, 血浆样品用乙酸乙酯提取浓缩检测, 进行LC-MS分析。结果 匹伐他汀在0.2~200.0 ng·mL^-1内线性关系良好(r=0.999 9)；平均提取回收率均为86.28%；日内日间RSD均小于12%。结论 本方法快速、简捷、准确，适用于匹伐他汀的临床药动学研究和血药浓度监测。

Abstract:

OBJECTIVE To establish an LC-MS method for the determination of pitavastatin in the human plasma. METHODS Pitavastatin and internal standard (IS, rosuvastatin) were separated on a Shim-pack C18 column. The mobile phase consisted of methanol/water (A/B) with 0.025% aqueous ammonia and 0.05 mmol·L^-1 ammonium acetate. Gradient elution mode was established. The samples were extracted with ethyl acetate and determined by LC-MS with selected ion monitoring (SIM) mode. RESULTS The linear calibration curve was obtained in the concentration range of 0.2-200.0 ng·mL^-1 (r=0. 999 9), the average extraction recovery was 86.28% and the RSD of inter- and intra-day were less than 12%. CONCLUSION　The developed analytical method was proved accurate, rapid, convenient, and suitable for the determination of pitavastatin in the human plasma and pharmacokinetic studies of pitavastatin.