超高效液相色谱-串联质谱法测定大鼠血浆及组织中贝达喹啉浓度及其药动学考察

目的:建立超高效液相色谱-串联质谱(UPLC-MS/MS)法测定SD大鼠血液及组织中贝达喹啉的浓度,研究其在大鼠体内的药动学及组织分布.方法:采用UPLC-MS/MS联用技术,测定大鼠血液及组织中贝达喹啉的药物浓度,并利用DAS软件及非房室模型统计矩方法计算药动学参数.结果:贝达喹啉线性范围为0.1～500 ng·mL...

Determination drug concentration of betaquinoline in rat plasma and tissues by UPLC-MS/MS and its pharmacokinetics study

OBJECTIVE UPLC-MS/MS method was established to determine the concentration of beta quinolone in blood and tissues,and to study its pharmacokinetics and tissue distributionin in rats.METHODS UPLC-MS/MS method was used to detect drug concentration.The DAS software and non-compartmental model statistical moment method were used to calculate the pharmacokinetic parameters.RESULTS The linear range of bedaquiline was 0.1－500 ng·mL^-1,and the quantitative lower limit was 0.1 ng·mL^-1,and the quantitative limit was 0.1 ng·mL^-1.Bedaquiline of rats’ perfusion conforms to a one-compartment model,t_max=(4.02±0.38)h,C_max=(130.4±13.4)ng·mL^-1,AUC_0－t=(1 207.9±140.6)h·ng·mL^-1,AUC_0－∞=(1 369.2±116.3)h·ng·mL^-1,t_1/2=(11.0±1.0) h,ant the proportion of bdq in lung tissue was the highest.CONCLUSION UPLC-MS/MS method is sensitive,specific,simple,rapid and efficient.The metabolism of bedaquiline conforms to the one-compartment model,and the distribution of it has high specificity.The lung,liver,and heart are the main distribution tissues.