液相色谱-串联质谱法测定人血浆中匹伐他汀

目的:建立灵敏、快速的液相色谱-串联质谱(LC-MS-MS)法测定人血浆中匹伐他汀,并用于药动学研究。方法:血浆样品经乙腈沉淀蛋白后,以乙腈-5 mmol·L~(-1)醋酸铵溶液(90:10,V:V)为流动相,Zorbax XDB C_8柱分离。采用电喷雾电离源(ESI),以多反应监测(MRM)方式进行正离子检测。用于定量分析的离子分别为m/z 422→m/z 290(匹伐他汀)和m/z 515→m/z 276(内标,替米沙坦)。结果:测定血浆中匹伐他汀的线性范围为0.1～100μg·L~(-1),定量下限为0.1μg·L~(-1)。日内、日间精密度(RSD)均小于12.0%,准确度(RE)在±2.4%以内。结论:该方法选择性好、灵敏度高、操作简便,适用于匹伐他汀的临床药动学研究。

Determination of pitavastatin in human plasma by liquid chromatographytandem mass spectrometry

AIM:To develop a LC-MS-MS method for the determination of pitavastatin in human plasma and study the pharmacokinetics of pitavastatin.METHODS:Pitavastatin and telmisartan (internal standard) were isolated from plasma using protein precipitation with acetonitrile,and then separated on a Zorbax XDB C_8 column.The mobile phase consisted of acetonitrile-5 mmol·L~(-1) ammonium acetate (90:10,V:V),at a flow- rate of 0.6 mL·min~(-1).An API 4000 tandem mass spectrometer equipped with electrospray ionization was used as detector and was operated in the positive ion mode.Multiple reaction monitoring (MRM) using the precursor to product ion combinations of m/z 422→m/z 290 and m/z 515→m/z 276 was performed to quantify pitavastatin and the internal standard,respectively.RESULTS:The calibration curves were linear over the range of 0.1-100μg·L~(-1).The lower limit of quantifieation was 0.1μg·L~(-1).The intra-day and inter-day relative standard deviation (RSD) across three validation runs over the entire concentration range was less than 12.0%. The accuracy was within±2.4%.CONCLUSION:The method is sensitive,selective and proved to be suitable for clinical investigation of pitavastatin pharmacokinetics.