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抗HIV化学成分DB02在大鼠体内的初步药代动力学研究(PDF)

《云南中医学院学报》[ISSN:1000-2723/CN:53-1048/R]

期数:
2016年02期
页码:
15-21
栏目:
方药研究
出版日期:
2016-04-10

文章信息/Info

Title:
Preliminary Pharmacokinetics of Anti HIV Chemical Composition DB02 in Rats
作者:
齐欢1赵高琼234刘红斌234崔佳丽234张培培234周艺佳234何严萍5王京昆234△
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
Author(s):
QI Huan1 ZHAO Gaoqiong234 LIU Hongbin234 CUI Jiali234 ZHANG Peipei234ZHOU Yijia234 HE Yanping5 WANG Jingkun234
1. College of Pharmacy and Chemistry, Dali University, Dali 671000, China;2. Yunnan Bai Yao Group Innovation and R&D Center, Kunming 650111, China;3. Drug Safety Evaluation Center of Yunnan Institute of Materia, Kunming 650111, China;4. Yunnan Province Company Key Laboratory for TCM and Ethnic Drug of New Drug Creation, Kunming 650111, China;5. Key Laboratory of Medicinal Chemistry of Natural Resource, Yunnan University, Kunming 650091, China
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
Keywords:
HPLC-MS/MS plasma concentration pharmacokinetic parameters non-nucleoside reverse transcriptase inhibitors
分类号:
R285.1
DOI:
10.19288/j.cnki.issn.1000-2723.2016.02.005
文献标识码:
A
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/mL浓度范围内,线性关系良好,定量下限为4.60ng/mL(S/N≥10),对13.6,123,923ng/mL 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:C max=(513±69)μg/L;t 1/2=(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。
Abstract:
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/mL for DB02 in rat plasma, the lowest limit of quantification(LLOQ) was 4.60 ng/mL(S/N≥10), to study recoveries, precision and accuracy of DB02 QC for 13.6, 123, 923 ng/mL, each concentration’s recoveries were above 90%, intra-day and inter-day precision were less than 15%, accuracy was 93.34%~102.51%, to meet the chemical drugs non-clinical pharmacokinetic study technical guidelines’ requirements. Pharmaco-kinetic parameters of DB02 in rats were as follows: C max=(513±69)μg/L; t 1/2=(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. After 1.004mg/kg single intravenous administration of one single dose, distribution of DB02 in rats showed one compartment model.

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备注/Memo

备注/Memo:
* 基金项目: 国家自然科学基金(30960459);云南省科技计划项目(2009BC019) 收稿日期: 2016 - 03 - 01 作者简介: 齐欢(1991-),女,黑龙江大庆人,在读硕士研究生,研究方向:中药化学及有效成分活性和作用机制.△通信作者:王京昆,E-mail:wjkyimm@163.com;何严萍,E-mail:yphe@ynu.edu.cn
更新日期/Last Update: 2016-03-20