高效液相质谱联用研究伐昔洛韦人体生物等效性

 目的研究健康人po盐酸伐昔洛韦片后的药动学和生物等效性。方法20个健康受试者采用随机分组自身交叉对照试验设计,口服盐酸伐昔洛韦片600 mgHPLC-MS联用法测定血浆中代谢产物阿昔洛韦浓度,以BAPP程序计算其药动学参数和评价生物等效性。结果在选定的色谱/质谱条件下阿昔洛韦与内标及血浆杂质分离良好,在41.6～5.34×103μg·L^-1内线性良好。阿昔洛韦的相对回收率大于96.7%,日内和日间RSD小于10.2%。盐酸伐昔洛韦片受试制剂(T)和参比制剂(R)的主要药动学参数:t_max分别为(1.5±0.6)(T)和(1.5±0.6)h(R),ρ_max分别为(2.83×10³±7.76×10²)(T)和(2.72×10³±8.50×10²)μg·L^-1(R);t_1/2分别为(3.21±0.29)(T)和(3.23±0.30)h(R);AUC_0-14分别为(1.02×10⁴±2.03×10³)(T)和(9.91×10³±2.46×10³)μg·h·L^-1(R);盐酸伐昔洛韦片相对生物利用度为(104.5±14.0)%。结论用LC-MS测定血浆中代谢产物阿昔洛韦浓度,杂质无干扰,定量限低,重复性好,准确度高。受试的盐酸伐昔洛韦片与参比的盐酸伐昔洛韦片生物等效。

Bioequivalence Study of Valaciclovir in Human by HPLC-MS Assay

OBJECTIVE To study the pharmacokinetics and bioequivalence of valaciclovir in human.METHODS Twenty volunteers orally took the valaciclovir tablets with 2-way crossover design.The concentration of acyclovir,the metabolite of valaciclovir in plasma,was determined by HPLC-MS.The pharmacokinetic parameters were calculated by BAPP software.RESULTS The calibration curve was linear in the range from 41.6 to 5.34×10³ μg·L^-1.The relative recovery was more than 96.7%.The intra-and inter-RSDs were less than 10.2%.The main pharmacokinetic parameters of t_1/2,ρ_max,t_max and AUC_0-14 for the test tablet were(3.21±0.29) h,(2.83×103±7.76×102) μg·L^-1,(1.5±0.6) h and(1.02×104±2.03×103) μg·h·L^-1,respectively.The pharmacokinetic parameters of t^1/2,ρ_max,t_max and AUC_0-14 for the reference tablet were(3.23±0.30) h,(2.72×10³±8.50×10²) μg·L^-1,(1.5±0.6) h and(9.91×10³±2.46×10³) μg·h·L^-1,respectively.The relative bioavailability of the test tablet was(104.5±14.0)%.CONCLUSION The HPLC-MS method for the determination of acyclovir in plasma was proved to be sensitive,accurate and convenient.The reference and test tablets were bioequivalent.