LC-MS-MS法测定人血浆中阿托伐他汀浓度

Determination of Atorvastatin in human plasma by LC-MS-MS

目的 建立液质联用色谱法（LC-MS-MS）测定人血浆中阿托伐他汀（atorvastatin）浓度。方法 采用萃取法处理血浆样品进行LC-MS-MS分析。分析柱为美国Thermo公司Thermo BioBasic-C8柱（2．1mm×100mm，5μm）；流动相为乙腈（含0．1％甲酸）：水（含0．1％甲酸）=70：30；流速0．3ml／min；质谱条件：电喷雾离子化电离源ESI负离子检测，喷雾电压（SP）3500KV，鞘气（SGP）流速10Arb，辅助气（AGP）流速15Arb，毛细管温度（TEM）314℃；选择反应监测（SRM）分别测定阿托伐他汀和甲苯磺丁脲558→278m／z（30EV）和269→106m／z（22EV）。结果 阿托伐他汀在0．1～20μg／L检测浓度范围内呈良好线性关系（r〉0．99），最低定量限（LLOQ）为0．1μg/L，绝对回收率在70％以上，高中低3种浓度的日内和日间RSD≤15％。结论 该方法操作简便、灵敏、准确，适用于临床阿托伐他汀的血药浓度监测及I期临床试验。

Objective To establish a method for determining Atorvastatin in human plasma by LC-MS-MS. Methods Atorvastatin was extracted for determination by LC-MS-MS. Analytical column was Thermo BioBasic-Cs （2.1mm×100mm,5μm）. The mobile phase was acetonitrile（0.1% acid） ： water（0.1% acid） =70：30. Mass spectrum conditions was ESI performing in the SRM mode using target ions m/z 558→278（30EV）（ Atorvastatin ）, m/z269→106（22 EV）（tolbutamide）, SP 3 500 KV, SGP 10 Arb, AGP 15 Arb, TEM 314℃. Results The calibration curve was linear over the range of 0.1-20μg/L. The LLOQ of Atorvastatin in plasma was 0.1μg/L. The extracted recovery was 〉70%. The intra-and inter-day RSD were 〈 15%. Conclusion The method is sensitive, simple and accurate to determinate Atorvastatin plasma concentration and suitable to study phase I clinical test of Atorvastatin.