西罗莫司血药浓度测定方法的建立及在肝移植患者中的应用

目的建立高效液相色谱法测定西罗莫司血药浓度,测定该药在肝移植患者中的药代动力学参数。方法以沉淀-萃取法处理全血样品,采用Hypersil ODS C18(250 mm×4.6 mm,5μm)柱,柱温为50℃,乙腈-甲醇-水(7.5:62.5:30)为流动相,流速1.2 mL/min,以32-去甲基雷帕霉素为内标,在276 nm波长处,检测西罗莫司血药浓度,并应用此方法测定5例肝移植患者的西罗莫司血药浓度。结果全血中西罗莫司浓度在2.0～50.0ng/mL范围内线性良好(r=0.999 7),平均相对回收率为99.1%(n=5)。5例肝移植患者的Cmax为(12.66±4.1)ng/mL,t1/2为(19.2±11.2)h,tmax为(1.8±0.3)h。结论本方法快速、简便、准确,灵敏度高,重现性好,可用于肝移植患者的西罗莫司临床药物监测。

Determination of sirolimus in human whole blood by HPLC and the exploratory in liver transplantation

Objective To establish an HPLC method to determine the concentration of sirolimus in whole blood. Methods The whole-blood samples were pretreated by precipitation-extraction method,and sirolimus was determined by HPLC-UV.Hypersil ODS C18 analysis column(250 mm×4.6 mm,5 μm)was used,and the temperature was set at 50 ℃.The mobile phase was a mixture of acetonitrile-methanol-water(7.5:62.5:30)with a flow rate of 1.2 mL/min.The detection wavelength was set at 276 nm. Results The calibration curve was linear within the range 2.0～50 ng/mL(r=0.999 7).The mean relative recovery was 99.1%,and the mean absolute recovery was 82.2%(n=5).The intra-day and the inter-day relative standard deviation did not exceed 3.3% and 6.3% respectively.In the five transplantation receptors,Cmax was(12.66±4.1)ng/mL,t1/2 was(19.2±11.2)h,tmax was(1.8±0.3)h. Conclusion This method is simple,rapid,sensitive and suitable for therapeutic drug monitoring of sirolimus.