HPLC法测定人血浆中霉酚酸的浓度及药动学研究

目的:建立以高效液相色谱法测定人血浆中霉酚酸浓度的方法,并对其在人体内的药动学参数进行研究。方法:霉酚酸血浆样品经甲醇沉淀后直接进样测定,其中色谱柱为Symmetry Shield C18,流动相为乙腈-水-三乙胺(40∶60∶0.3),流速为1.0mL·min-1,柱温为30℃,测定波长为218nm,进样量为20μL。结果:霉酚酸检测浓度在0.2~50mg·L-1范围内与峰面积积分值线性关系良好(r=0.9996),定量下限为0.2mg·L-1;平均方法回收率为101.94%,平均提取回收率为87.06%;日内、日间RSD均<6%。另,人体药动学研究表明,霉酚酸在体内存在肠肝循环导致双峰出现,人体过程符合单室开放模型。结论:本方法简便、灵敏、专一、准确、精密,可用于霉酚酸的药动学研究。

Determination of Mycophenolic Acid in Human Plasma by HPLC and Study of Its Pharmacokinetics

OBJECTIVE:To establish a HPLC method for the determination of mycophenolic acid (MPA) in human plasma and to study its pharmacokinetics in human body.METHODS:After sedimentation by methanol,plasma sample of MPA was determined directly on Symmetry Shield C18 column with column temperature at 30℃,detective wavelength at 218mn and sample size at 20μL.The mobile phase consisted of acetonitrile-water-triethylamine(40∶60∶0.3) with a flow rate of 1.0mL·min-1.RESULTS:The calibration curve was linear over the range of 0.2～50mg·L-1(r=0.999 6)and the limit of quantitation was 0.2mg·L-1.The mean methodological recovery was 101.94% and the mean extraction recovery was 87.06%.The RSD of both the intra-day and the inter-day were less than 6%.The pharmacokinetic study showed that MPA had enterohepatic circulation in human body,which resulted in the occurrence of double peaks,and the concentration-time curves of MPA were fitted to one-compartment open model.CONCLUSION:This method is sensitive,rapid,specific,accurate and precise,and can be used for the study of pharmacokinetics of MPA.