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目的建立高效液相色谱-质谱联用法测定人血浆中阿托伐他汀及代谢产物的质量浓度。方法用固相萃取法处理血浆,用XTerraMS C18色谱柱,以95%乙腈-5 mmol·L-1碳酸氢铵为流动相,梯度洗脱,用正离子扫描,多反应监测方式测定样品中药物的质量浓度,检测专属性、标准曲线与定量下限、精密度与回收率、基质效应和稳定性。结果血浆样品中,阿托伐他汀、邻羟基化阿托伐他汀、对羟基化阿托伐他汀的回归方程分别为Y=1.82X-2.94×10-3(r=0.999 5),Y=0.28X-4.14×10-5(r=0.999 7),Y=0.60X+1.11×10-3(r=0.997 4);阿托伐他汀及代谢产物在0.1~40.0 ng·m L-1线性关系良好,定量下限为0.1 ng·m L-1。血样日内与日间RSD均小于15%,平均回收率>80%,且稳定性均较好。结论本方法简便快速、灵敏准确、特异性强,适用于阿托伐他汀及代谢产物的体内药代动力学研究。
Objective To establish a method for the determination of atorvastatin and its metabolites in human plasma by high performance liquid chromatography-mass spectrometry. Methods Plasma was processed by solid-phase extraction. The samples were eluted with XTerra MS C18 column using 95% acetonitrile-5 mmol·L -1 ammonium bicarbonate as the mobile phase. The sample was determined by positive ion scanning and multi-reaction monitoring The quality of the drug concentration, detection specificity, the standard curve and lower limit of quantification, precision and recovery, matrix effect and stability. Results The regression equations of atorvastatin, o-hydroxy-atorvastatin and para-hydroxylated atorvastatin were Y = 1.82X-2.94 × 10-3 (r = 0.999 5) and Y = 0.28 X-4.14 × 10-5 (r = 0.999 7), Y = 0.60X + 1.11 × 10-3 (r = 0.997 4) .The linear relationship between atorvastatin and metabolites in the range of 0.1-40.0 ng · m L -1 Good, with a lower limit of quantitation of 0.1 ng · m L-1. The RSDs of blood samples were both less than 15% and the average recovery was> 80%. The stability was good. Conclusion The method is simple, rapid, accurate, sensitive and specific. It is suitable for in vivo pharmacokinetic study of atorvastatin and its metabolites.