液相色谱-串联质谱法测定人血浆中盐酸度洛西汀的浓度及其药代动力学研究

目的建立高效液相色谱-串联质谱联法测定人血浆中度洛西汀(抗抑郁药)并研究其在健康人体的药代动力学。方法5名男性与5名女性健康志愿者口服盐酸度洛西汀肠溶片60mg,色谱柱为phenomenex C18,流动相为水相(5mmol.L-1醋酸胺,含0.02%的甲酸)-乙腈=55∶45;电喷雾电离源正离子模式(ESI+),以氟西汀为内标。用高效液相色谱-串联质谱法测定盐酸度洛西汀血药浓度,并计算药代动力学参数。结果度洛西汀血浆浓度在0.89～106.80ng·mL-1内与峰面积积分值线性关系良好(γ=0.9977)。方法回收率在93.19%～107.27%,萃取回收率在72.81%～89.96%。日内、日间标准偏差均小于11%。主要药代动力学参数:Cmax为(44.40±17.78)ng·mL-1,tmax为(6.10±1.29)h,t1/2为(12.81±2.31)h;AUC0-60和AUC0-∞分别为(696.04±337.82),(733.82±343.40)ng.h.mL-1。结论本方法操作简单,结果准确可靠,适于度洛西汀的血药浓度监测和药代动力学研究。

Determination concentration of duloxetine hydrochloride in human plasma by HPLC-MS/MS and study on its pharmacokinetics

Objective To establish a liquid chromatography-tandem mass spectrometry(LC-MS/MS)method for the determination concentration of duloxetine in human plasma and study on its pharmacokinetics in healthy human.Methods The separation of duloxetine was performed on Phenomenex C_(18) column with fluoxetine as the internal standard.The mobile phase was composed of 5 mmol L~(-1) ammonium acetate with 0.02% formic acid acetonitrile(55:45).Electrospray ionization source was applied and operated in positive ion mode.A single dose of 60 mg duloxetine hydrochloride was given to 5 male and 5 female healthy volunteers and the plasma was separated.The concentration of duloxetine was determined by HPLC-MS/MS and the pharmacokinetic parameters were calculated.Results The linear range of duloxetine was 0.89-106.80 ng·mL~(-1)(γ=0.9977).The methodological recovery and the extraction recovery ranged between 93.19%-107.27% and 72.81%-89.96%,respectively.Both the inter-day RSD and intra-day RSD were less than 11%.The main pharmacokinetic parameters after a single dose of 60mg duloxetine are as follows: C_(max) was(44.40 ±17.78)ng·mL~(-1),t_(max) was(6.10±1.29)h,t_(1/2) was(12.81 ±2.31)h;AUC_(0-60) and AUC_(0-∞) were (696.04±337.82),(733.82±343.40)ng·h·mL~(-1),respectively.Conclusion The method is simple,accurate and reliable,and suitable for the determination of duloxe-tine in therapeutic drug monitor and its pharmacokinetics study.