高效液相色谱-质谱联用法测定人血浆中瑞舒伐他汀的浓度

Determination of Rosuvastatin concentration in human plasma by HPLC-MS/MS

目的建立HPLC-MS/MS方法定量测定人血浆中瑞舒伐他汀浓度。方法用液液萃取法处理血浆,以瑞舒伐他汀-D6为内标,色谱柱:ThermoHypersI I GOLD柱(2.1 mm×100 mm,3.0μm),柱温:40℃,流动相:甲醇-0.1%甲酸+5 mmol·L^(-1)甲酸铵水溶液,等度洗脱,流速:0.35 mL·min^(-1)。用正离子扫描,多反应监测方式(MRM)测定样品中药物的质量浓度。考察该方法的专属性、标准曲线与定量下限、精密度与准确度、回收率、基质效应和稳定性。结果血浆样品中瑞舒伐他汀回归方程为y=3.29×10^(-1)x-3.46×10^(-3)(r=0.998 8),瑞舒伐他汀在0.05~25.00 ng·mL^(-1)内线性关系良好,定量下限为0.05 ng·mL^(-1)。日内、日间精密度的RSD均<15%,平均回收率>95%,稳定性较好。结论本方法简便快速、特异性强、灵敏准确,适用于人体血浆中瑞舒伐他汀浓度的测定。

Objective To determine the rosuvastatin concentration in human plasma by establishing HPLC-MS/MS method. Method The plasma was treated with liquid-liquid extraction,using rosuvastatin-D6 as internal standard. Chromatographic column： ThermoHypersI I GOLD（ 2. 1 mm × 100 mm,3. 0 μm）,column temperature： 40 ℃,mobile phase： Methanol-0. 1% formic acid and 5 mmol·L^-1 ammonium formate,isocratic elution,flow rate： 0. 35 mL ·min^-1,mass concentration of the sample was measured with positive ion scan and multiple reaction monitoring mode. The specificity,lower limit of quantitation,standard curve,precision and accuracy,recovery and stability as well as the matrix effect were investigated. Result The standard curve of rosuvastatin was y = 3. 29 × 10^-1x-3. 46 × 10^-3（ r = 0. 998 8）,and rosuvastatin had good linear relationship in 0. 05-25. 00 ng·mL^-1,the lower limit of quantitation of the methodwas 0. 05 ng·mL^-1. Intra-day and inter-day RSD of the plasma samples were less than 15%,the average recovery was 〉95%,and stability was good. Conclusion The method is simple,rapid,sensitive and accurate,specific,which is suitable for the determination of rosuvastatin concentration in human plasma.