LC-MS/MS法测定人血浆中洛伐他汀及其活性代谢物的含量  

Determination of Lovastatin and Its Active Metabolites in Human Plasma with High Performance Liquid Chromatography-tandem Mass Spectrometry

作　　者：廖冬雪[1] 秦永平[1] 龚晓丽[1] 梁茂植[1] 余勤[1] 南峰[1] 向瑾[1] 

机构地区：[1]四川大学华西医院临床药理研究室,成都610041

出　　处：《四川大学学报（医学版）》2009年第4期730-733,共4页Journal of Sichuan University(Medical Sciences)

摘　　要：目的建立高效液相色谱-串联质谱法(LC-MS/MS)测定人血浆中洛伐他汀及其活性代谢物洛伐他汀酸的浓度。方法样品用乙酸乙酯∶二氯甲烷(体积比为1∶1)提取浓集后进样,色谱柱为Phenomenex Gemini C18(50×3mm,3μm),流动相为乙腈-水(85∶15)。质谱采用ESI离子源MRM模式检测,以辛伐他汀为内标,按内标法定量。洛伐他汀、洛伐他汀酸和内标的检测离子对分别为质荷比(m/z)427.4→325.4、445.4→343.4和436.4→325.4。结果洛伐他汀在0.031～64μg/L范围内线性关系良好(r=0.9987),最低定量限为0.031μg/L,方法回收率在96%～102%之间,日内、日间精密度相对标准偏差(RSD)分别小于5.3%及9.3%。结论本文建立的方法准确、灵敏,可用于洛伐他汀血药浓度测定及药代动力学研究。Objective To develop a sensitive LC-MS/MS method for analyzing lovastatin and its active metabolites lovastatin acid in human plasma. Methods Lovastatin and lovastatin acid were extracted from plasma by ethyl ether -dichloromethane （V/V, 1 ： 1）, with simvastatin serving as an internal standard. The analytes went through the column of Phenomenex Gemini Cl8 （50 × 3 mm, 3 μm） with mobile phase acetonitrile-water （85： 15）, and was analyzed by API3000 after protonated with ESI mode. The ion pairs being detected were 427.4→325.4, 445.4→343.4 and 436.4→325.4, respectively. Results The established method was able to determine lovastatin in human plasma over the range of 0. 03125-64 μg/L, with recovery rates ranging from 96% to 102 %. The intra and inter day variances were below 9.3%. Conclusion The LC-MS/MS method for analyzing lovastatin is validated and is suitable for clinical pharmaeokinetic studies.

关 键 词：高效液相色谱-串联质谱法 洛伐他汀 血药浓度代谢物 洛伐他汀酸 

分 类 号：R96[医药卫生—药理学]