抗HIV化学成分DB02在大鼠体内的初步药代动力学研究  

Preliminary Pharmacokinetics of Anti HIV Chemical Composition DB02 in Rats

作　　者：齐欢 赵高琼 刘红斌 崔佳丽 张培培 周艺佳 何严萍[5] 王京昆 

机构地区：[1]大理大学药学与化学学院,云南大理671000 [2]云南白药集团创新研发中心,云南昆明650111 [3]云南省药物研究所药物安全性评价中心,云南昆明650111 [4]云南省中药和民族药新药创制企业重点实验室,云南昆明650111 [5]云南大学化学科学与工程学院,教育部自然资源药物化学重点实验室,云南昆明650091

出　　处：《云南中医学院学报》2016年第2期15-21,共7页Journal of Yunnan University of Traditional Chinese Medicine

基　　金：国家自然科学基金(30960459);云南省科技计划项目(2009BC019)

摘　　要：目的建立大鼠血浆中DB02的高效液相色谱质谱联用（HPLC-MS/MS）检测方法,并进行DB02的大鼠尾静脉注射给药药代动力学研究。方法 6只Sprague Dawley（SD）大鼠,雌雄各半,尾静脉注射DB02增溶溶液1.004mg/kg·bw,分别于不同时间点眼底静脉丛取血,HPLC-MS/MS测定各时间点大鼠血药浓度,应用DAS2.0计算药代参数。结果所建立的检测方法在4.60~930ng/m L浓度范围内,线性关系良好,定量下限为4.60ng/m L（S/N≥10）,对13.6,123,923ng/m L 3个浓度的DB02大鼠血浆质控样品进行回收率、精密度与准确度考察,各浓度回收率均在90%以上,日内与日间精密度均小于15%,准确度为93.34%~102.51%,符合《药物非临床药代动力学研究技术指导原则》要求。大鼠尾静脉注射DB02后药代参数如下：Cmax=（513±69）μg/L;t1/2=（33.4±5.3）min;AUC（0-t）=（8.15±0.06）mg/L＊min。结论实验所建立的HPLC-MS/MS分析方法简单、快速、准确,能够满足DB02在大鼠体内的药代动力学的研究要求。按照1.004mg/kg单剂量单次静脉给药后,DB02在大鼠体内的血药浓度-时间曲线呈一房室模型。Objective To establish the measurement method of DB02 in rat plasma by HPLC-MS/MS,operating the pharmacokinetic studies of DB02 in rat after tail vein injection. Methods Six Sprague Dawley（SD）rats divided into male and female were administrated by intravenous injection of a solution DB02 1.004mg/kg·bw,rat retinal venous plexus bloods were collected at different time points,the drug concentrations of plasma were determined by HPLC-MS/MS,calculating the main pharmacokinetic parameters by DAS2.0. Results The method exhibited a linear range of 4.60~930 ng/m L for DB02 in rat plasma,the lowest limit of quantification（LLOQ） was 4.60 ng/m L（S/N≥10）,to study recoveries,precision and accuracy of DB02 QC for 13.6,123,923ng/m L,each concentration＇s recoveries were above 90%,intra-day and inter-day precision were less than 15%,accuracy was93.34% ~102.51%,to meet the chemical drugs non-clinical pharmacokinetic study technical guidelines＇ requirements. Pharmaco-kinetic parameters of DB02 in rats were as follows：Cmax=（513±69）μg/L;t1/2=（33.4±5.3）min;AUC（0-）t=（8. 15±0. 06）mg/L·min.Conclusions HPLC-MS/MS was simple,rapid,accurate,and able to meet the pharmacokinetic repuirements of DB02 in rats. After1.004mg/kg single intravenous administration of one single dose,distribution of DB02 in rats showed one compartment model.

关 键 词：高效液相色谱质谱联用 血药浓度 药代动力学参数 非核苷类 逆转录酶抑制剂 

分 类 号：R285.1[医药卫生—中药学]