摘要
目的:建立人血浆中替诺福韦浓度的LC-MS/MS测定法,并用于富马酸替诺福韦二吡呋酯片的药动学和生物等效性研究。方法:采用自身双交叉试验设计,20例男性健康受试者随机分成2组,分别空腹口服受试制剂或参比制剂300 mg,0～72 h间隔采集血样。以LC-MS/MS法测定血浆替诺福韦浓度,DAS2.1.1计算药动学参数。结果:建立的LC-MS/MS法在2～1 200 ng.mL-1范围内线性关系良好,最低定量限为2 ng·mL-1,批内及批间精密度RSD均小于15%。受试制剂与参比制剂的Tmax均为(0.5±0.2)h,Cmax分别为(604±207)和(573±189)ng.mL-1,t1/2分别为(17.1±2.9)和(17.4±4.0)h,AUC0～72 h分别为(2 490±604)和(2 297±499)h·ng·mL-1。结论:建立的LC-MS/MS法准确可靠,富马酸替诺福韦二吡呋酯片两种制剂生物等效。
Objective ： To establish a LC-MS/MS method for the determination of tenofovir in human plasma and study the pharmacokinetics and bioequivalence of tenofovir disoproxil fumarate tablets. Methods： In a randomized two-way crossover study,20 healthy male volunteers were divided into two groups, and were administered re- spectively with a single oral dose of test and reference preparations containing 300 mg of tenofovir disoproxil fumar- ate after an over-night fast. The blood samples were collected at predetermined time intervals up to 72 hours. The plasma concentration of tenofovir was determined by LC-MS/MS. The pharmacokinetic parameters were estimated by DAS 2.1.1. Results：The established LC-MS/MS method had linear calibration range over 2 - 1 200 ng·mL^-1 with a LLOQ of 2 ng·mL^-1 for tenofovir in human plasma. The intraand inter-batch standard deviations were less than 15%. The pharmacokinetic parameters for the test and reference tablets were as follows：Tmax both （0.5±0. 2） h, Cmax（604±207 ） and （573±189 ） ng·mL^-1, t1/2 （ 17. 1±2.9 ） and （ 17.4± 4.0 ） h, AUC0-72h （ 2 490±604 ） and （2 297±499 ） h·ng·mL^-1, respectively. Conclusion ： The method is suitable for the pharmacokinetic study of teno-fovir disoproxil fumarate tablets. The two preparations are bioequivalent.
出处
《中国新药杂志》
CAS
CSCD
北大核心
2013年第6期686-690,共5页
Chinese Journal of New Drugs
