LC-MS/MS定量测定人体血浆中阿托伐他汀浓度

Quantitative Determination of the Atorvastatin Concentration in Healthy Human Plasma by LC-MS/MS

目的：建立定量测定人体血浆中阿托伐他汀浓度的HPLC-MS/MS的方法。方法：以吲哚美辛为内标,采用Shim-pack VP-ODS柱（150×2.0 mm I.D.,5μm,日本Shimadzu Technologies Inc.公司）为固定相;乙腈-0.5%甲酸溶液（90：10,v/v）为流动相,流速为0.3 ml/min;通过电喷雾离子源（ESI）,以正离子多反应监测模式进行检测。阿托伐他汀与内标用于检测的离子对分别为m/z 559.4 m/z 250.3和m/z 358.3 m/z 139.2。结果：阿托伐他汀在0.10~20.00 ng/ml范围内与峰面积比值线性范围良好（r=0.9962）,定量下限为0.10 ng/ml,日内日间精密度的RSD均小于12%,平均回收率大于71%。结论：所建方法准确度高,方法灵敏,专属性强且操作简便,可适用于阿托伐他汀的血药浓度测定和临床药代动力学研究。

Objective： To establish the HPLC-MS/MS method to quantitatively determine the concentration of atorvastatin in healthy human plasma.Methods： The concentration was detected by Multiple Reaction Monitoring（MRM） in positive mode using Electrospray Ionization（ESI） source,with indomethacin as internal standard,Shim-pack VP-ODS（150×2.0 mm I.D.,5 μm,Shimadzu Technologies Inc.,Japan） as immobile phase and Acetonitrile-0.5 % Formic Acid aqueous solution as mobile phase（the flow rate was 0.3 ml/min）.The ion pair was m/z 559.4 m/z 250.3 for atorvastatin and m/z 358.3 m/z 139.2 for indomethacin.Results： The calibration curve for plasma atorvastatin was linear in the range of 0.10~20.00 ng/ml（r=0.9962）,the lower limit of quantitation was 0.10 ng/ml,the inter-and intra-day precision（RSD） were both less than 12 %.The average recovery rate was above 71 %.Conclusion： This method is accurate,sensitive,specific and convenient,and could be used in the determination of plasma atorvastatin concentration and the clinical study of its pharmacokinetics.