中文摘要：

目的建立同时检测人血浆中霉酚酸（MPA）及其葡糖苷酸代谢物浓度的高效液相色谱法（HPLC），并将其应用于肾移植术后患者霉酚酸酯（MMF）的治疗药物监测。方法以蛋白沉淀剂甲醇-5％硫酸锌（70：30，V：V）溶液进行血浆样品药物提取；内标物为萘普生；色谱柱为C18（4．6mm×250mm，5μm）；流动相为甲醇-水（含0．1％三氟乙酸）（65：35，V：V）；流速0．8mE／rain；检测波长215nm。结果MPA与其葡糖苷酸代谢物MPAG的线性范围分别为0．1—50mg／L及0．5—200mg／L，r2〉0．999；绝对回收率分别为63．95％～83．76％及57．14％-66．19％；两者日间及日内的相对标准偏差（RSD）均小于10％。6例。肾移植术后早期患者服用1．5g/d霉酚酸酯胶囊达药物稳态后，MPA及MPAG的Tmax分别为（1．08±0．74）h及（2．58±1．24）h，Cmax分别为（21．33±8．61）mg／L及（106．98±31．91）mg／L，AUC0-t分别为（58．73±16．26）及（833．32±215．03）mg·L^-1·h^-1。结论HPLC检测方法准确、灵敏、特异性好，并成功应用在。肾移植术后早期患者的治疗药物监测（TDM）中。

英文摘要：

Objective To establish a high-performance liquid chromatography method for simuhaneous determination of mycophenolic acid（MPA） and its 7-O-glucuronide metabolite（MPAG） in human plasma and to study pharmacokinetics of MPA in Chinese renal transplant recipients after administration of mycophenolate mofetil（MMF）. Methods Plasma protein was precipitated with methanol ： 5% ZnSO4 （ 70 ： 30, V ： V）, using naproxen as internal standard. The separation was conducted with C18 column（4.6mm×250mm,5μm）. The mobile phase was a mixture of methanol and 0.1% trifluoroacetic acid（65 ： 35, V ： V） and the flow rate was 0. 8ml/min. Wavelength of detection is 215 nm. Results The calibration curve was hnear in the range of 0.1 - 50mg/L for MPA and 0. 5 - 200nag/L for MPAG（ r2 〉 0.999）. The absolute recoveries for MPA and MPAG were 63.95% - 83.76% and 57.14% - 66.19% , respectively. The RSD of intra-and inter-day were all less than 10%. The steady-state pharmacokinetic parameters of MPA and MPAG after 1.5g/d administration of MMF in 6 early-stage renal transplant recipients were as follows：Tmax was（ 1.08±0.74） h and（2.58 ± 1.24） h,Cmax was（21.33 ± 8. 61 ）mg/L and（ 106.98 ±31.91 ） rag/L, AUC0-t was （58.73±16.26）mg·L^-1·h^-1 and（833.32 ±215.03）mg ·L^-1·h^-1,respectively. Conclusion This method was accurate, sensitive and specific and it was successfully applied in therapeutic drug monitoring （TDM） of mycophenolate mofetil in early-stage renal transplant recipients.