血浆中去羟肌苷测定与制剂生物等效性评价  

Determination of Didanosine in Human Plasma and Its Application to a Bioequivalence Study

作　　者：靳凤丹[1] 陈笑艳[2] 于河舟 安晓霞 钟大放[2] 

机构地区：[1]沈阳药科大学药物代谢与药物动力学实验室,沈阳110016 [2]中国科学院上海药物研究所,上海201203 [3]东北制药总厂,沈阳110026

出　　处：《中国药学杂志》2006年第13期1016-1019,共4页Chinese Pharmaceutical Journal

摘　　要：目的 建立测定人血浆中去羟肌苷的液相色谱-质谱／质谱联用法（LC-MS／MS），并应用于药物制剂生物等效性评价。方法 18名中国健康男性志愿者单剂量随机交叉po 200mg去羟肌苷参比制剂和受试制剂，血浆样品经沉淀蛋白处理，通过LCMS／MS测定其浓度，采用非隔室模型计算药动学参数和相对生物利用度，并对参数进行方差分析和双单侧t检验。结果 LCMS／MS测定血浆中去羟肌苷的线性范围为5．0-2000μg·L^-1，定量下限为5．0μg·L^-1。日内、日间精密度（RSO）均小于6％，准确度（RE）在±4％之内。应用本法测得18名中国健康男性志愿者po 200mg去羟肌苷参比制荆后主要药动学参数为：tmax，为（0．65±0．30）h，ρmax为（1052±353）μg·L^-1，t1／2为（1．53±0．38）h，用梯形法计算，AuC0-t为（1628±479）μg·h·L^-1，服用受试制剂后主要药动学参数为：tmax为（0．47±0．13）h，ρmax为（1090±531）μg·L^-1，t1／2为（1、44±0．46）h，Auq。为（1520±661）μg·h·L^-1。以AUC0-t计算相对生物利用度为（95．8±20．8）％。结论 该法灵敏、快速、准确，操作简便、线性范围宽，适用于去羟肌苷制剂的生物等效性评价。OBJECTIVE To develop a sensitive and specific LC-MS/MS method for the determination of didanosine in human plasma and to study the bioequivalence of different formulations containing didanosine. METHODS After a simple protein precipitation using acetonitrile, the samples were analyzed by liquid chromatography-tandem mass spectrometry. The pharmacokinetic parameters of didanosine in two formulations were calculated by non-compartment analysis. RESULTS The linear calibration curves were obtained in the concentration range of 5.0 - 2 000 μg·L^-1. The intm- and inter-day relative standard deviations （RSD） over the entire concentration range were less than 6%. Accuracy （RE） determined at three concentrations was within± 4%. Pharmacokinetic parameters for the reference formulation were obtained as follows： tmax was （0.65±0.30） h, ρmax= was （1 052±353） μg·L^-1, t1/2 was （1.53±0.38） h, AUC0-t, was （1 628±479） pg·h·L^-1 Pharmacokinetic parameters for the lest formulation were obtained as follows： tmax was （0.47 ± 0.13） h, ρmax was （ 1 090 ± 531 ） μg·L^-1, t1/2 was （ 1.44 ± 0.46） h , AUC0-t was （ 1 520 ± 661 ） μg·h·L^-1 .The relative bioavailability of the test formulation to the reference was （95.8 ± 20.8） %. CONCLUSION The method is sensitive, rapid, robust, and is proved to be suitable for bioequivalence evaluation of formulations containing didanosine.

关 键 词：去羟肌苷 液相色谱-质谱-质谱联用法 生物等效性 

分 类 号：R969.1[医药卫生—药理学]