反相高效液相色谱法测定茚地那韦2种制剂在健康人体的相对生物利用度(英文)

目的:建立高效液相色谱法测定血浆中茚地那韦2种制剂的浓度,并比较相对生物利用度。方法:采用反相高效液相色谱法测定18名男性健康受试者单剂量交叉口服800 mg两种茚地那韦胶囊后不同时间血浆中的药物浓度。萃取溶剂为乙腈。色谱条件:Hypersil ODS C18,流动相为乙腈∶0.01 mol.L-1磷酸盐缓冲液(pH 5.5)=43∶57。检测波长为210 nm。线性范围为0.03~16.38 mg.L-1。结果:两者药-时曲线均符合一房室模型。试验制剂和参比制剂的药动学参数如下:cmax分别为(10.6±s2.4)mg.L-1和(9.8±2.2)mg.L-1;tmax分别为(0.71±0.19)h和(0.8±0.3)h;t12ke分别为(1.30±0.24)h和(1.31±0.23)h;AUC0~10分别为(23±6)mg.h.L-1和(22±5)mg.h.L-1;AUC0~∞分别为(24±6)mg.h.L-1和(22±5)mg.h.L-1。双向单侧t检验证明,两制剂的主要药动学参数无明显差异。结论:所建立的HPLC法适用于测定人血浆中茚地那韦的浓度,试验制剂与参比制剂具有生物等效性。

Relative bioavailability of two formulations of indinavir in Chinese healthy volunteers by reversed phase high performance liquid chromatography

AIM: To establish a method to determine the concentration of indinavir in human plasma and study indinavir bioavailability in Chinese healthy people. METHODS: In a random two-period crossover study, 18 healthy male volunteers received a single dose of indinavir capsules 800 mg of two formulations respectively.A sensitive and specific reversed phase HPLC method was developed to quantitate plasma levels of indinavir. The drug was extracted from plasma with acetonitrile. Analysis was performed on a Hy persil C18 column with a mobile phase of acetonitrile:0.01 mol · L -1 phosphate buffer(pH 5.5 ) (43: 57).The UV detector was set at 210 nm. The standard curve covered the concentration ranged from 0. 03 to 16.38 mg · L-1. RESULTS: The concentration-time curves of reference and tested formulations both fitted to a one-compartment open model. The main pharmacokinetic rameters of tested and reference formulations were (10.6 ±s 2.4) mg· L-1 and (9.8 ±2.2)mg· L-1 for cmax, (0. 71 ± 0. 19) h and (0. 8 ±0.3) h for tmax, (1.30±0.24) h and (1.31 ±0.23) h for t1/2ke, (23±6) mg·h· L-1 and (22±5) mg·h · L-1 forAUC0-10, (24±6) mg · h · L-1 and (22±5) mg · h · L-1 for AUC0-∞, respectively. Two one-sidet test and variance analysis were performed in bioequivalent assessment. No statistically significant difference was found in AUC0-10, AUC0-∞ and cmax values between the tested and reference formulations. CONCLUSION:The reversed phase HPLC is a reliable method to determine the concentration of indinavir in human plasma and the two formulations of indinavir are bioequivalent.