中国西部健康人群口服恩曲他滨胶囊的药动学

Pharmacokinetics of emtricitabine capsule in healthy volunteer from western China

目的:建立固相萃取-高效液相色谱法测定人血浆中恩曲他滨含量的方法,并研究口服恩曲他滨胶囊在中国西部健康人群的药动学特征。方法:以拉米夫定为内标,选择固相萃取柱提取样品,在分离柱上,以甲醇-含0.08%三乙胺的20mmol.L-1磷酸二氢钾水溶液(稀磷酸调pH3.5)为流动相,采用梯度洗脱,检测波长为279 nm。结果:血浆中内源性物质对恩曲他滨的测定无干扰,最低检出限为7 ng.mL-1,恩曲他滨在10～5 000 ng.mL-1范围内线性关系良好,r=0.999 8。绝对回收率为93.5%～96.7%,方法回收率为93.1%～97.6%,日内精密度RSD≤6.1%,日间精密度RSD≤7.4%。结论:本方法处理简单,无干扰,灵敏度高,中国西部人群单独给予恩曲他滨胶囊的的血浆半衰期明显缩短,替诺福韦和高脂食物使得恩曲他滨血浆浓度的达峰时间明显延迟,其他药动学参数基本不变。

OBJECtIVE To establish a method for determination of emtricitabine in human plasma and study the pharmaco-kinetics of emtricitabine capsule in healthy volunteers from western China by HPLC. METHODS Lamivudine was employed as an internal standard. Emtricitabine in human plasma was extracted by a C18 solid phase extraction（SPE）. Hypersil CK）LD C18 （4. 6 mm ×250 mm, 5μm） was used as an analytical column and methanol-20 mmol. L -1 potassium dihydrogen phosphate（adjusted pH to 3. 5 with orthophosphoric acid） as mobile phase. The detection wavelength was 279 nm. RESULTS Emtricitabine was separated completely without interference. The concentration range of standard curve was 10 - 5 000 ng-mL 1 （r = 0. 999 8,n = 5）. The delection limit of emtricitabine in plasma was 7 ng.mL-1. The absolute recovery was 93.5% - 96. 7%, the analytical recovery was 93. 1% - 97. 6%, the within-day RSD and inter-day RSD were less than 6. 1% and 7. 4% respectively. CONCLUSION This method is sample and sensitive,and can be used in analyzing emtricitabine in biological sample. Phar macokinetic characteristics of emtricitabine in Chinese healthy people are similar to that of the foreign crowds.