LC-MS法测定人血浆中瑞舒伐他汀的浓度  

Determination of Rosuvastatin Concentration in Human Plasma by LC-MS Method

作　　者：赵婷[1,2] 张丹[2] 郑天雷[2] 王晓琳[1,2] 王涛[2] 王唯红[1] 刘会臣[2] 

机构地区：[1]山东大学药学院药物分析教研室,济南市250012 [2]航天中心医院临床药理室,北京市100049

出　　处：《中国药房》2011年第46期4368-4371,共4页China Pharmacy

摘　　要：目的:建立测定人血浆中瑞舒伐他汀浓度的液-质联用(LC-MS)法。方法:人血浆样本以乙醚-二氯甲烷(3∶2)液-液萃取后,采用LC-MS法进行测定,其中色谱柱为Shim-Pack VP-ODS,流动相为甲醇-5mmol.L^(-1)乙酸铵溶液(含0.5%甲酸)(65∶35),流速为0.3mL.min^(-1);选用API3200型三重四极杆串联质谱仪的多重反应监测(MRM)扫描方式进行监测,电喷雾离子化源,正离子方式,选择监测离子反应分别为m/z482.2→258.2(瑞舒伐他汀)和m/z748.5→158.4(内标,克拉霉素)。结果:瑞舒伐他汀和克拉霉素的保留时间分别为3.49min和2.70min;血浆中瑞舒伐他汀的线性范围为0.0500～30.0ng·mL^(-1)(r=0.9962),定量下限为0.0500ng·mL^(-1);日内、日间RSD均<11%;平均提取回收率为(89.7±3.6)%;稳定性试验中,在各种贮存条件下血浆中瑞舒伐他汀均稳定。结论:该方法快速、灵敏、准确、专属性强,适用于人血浆中瑞舒伐他汀浓度的测定及瑞舒伐他汀钙制剂的人体生物等效性研究。OBJECTIVE：To establish the method for the LC-MS determination of rosuvastatin concentration in human plasma.METHODS：After liquid-liquid extraction with aether-dichloromethane（3∶2）,LC-MS method was adopted.The determination were separated on a Shim-Pack VP-ODS column with the mobile phase consisted of methanol-5 mmol·L^（-1）ammonium acetate solution（containing 0.5% formic acid）（65∶35）at a flow rate of 0.3 mL·min-1.Detection was carried out by electrospray positive ionization mass spectrometry in the multiple reaction monitoring（MRM）mode.The MRM transitions of m/z 482.2→258.2 and m/z 748.5→158.4 were used to quantify rosuvastatin and I.S.,respectively.RESULTS：Rosuvastatin and I.S.were eluted for 3.49 min and 2.70 min,respectively.The calibration curve was linear in the range of 0.050 0 ng·mL-1～30.0 ng·mL^（-1）（r=0.996 2）with the lower limit of quantitation（LLOQ）of 0.050 0 ng·mL^（-1）.Intra-day and inter-day RSD were both less than 11%.Mean extraction recoveries were（89.7±3.6）%.In the stability studies,rosuvastatin in plasma was found to be stable under various storage conditions.CONCLUSION：It is a rapid,sensitive,selective and reliable method for the determination of rosuvastatin concentration in human plasma.The method is suitable for bioequivalence study of rosuvastatin calcium preparations in human subjects.

关 键 词：瑞舒伐他汀 血药浓度 液-质联用法 生物等效性 

分 类 号：R969.3[医药卫生—药理学] R972.6[医药卫生—药学]