摘要
建立LC-MS/MS法测定嘧啶核苷类化合物GY005在大鼠血浆中的浓度,并应用于大鼠体内的药代动力学研究.以特非那定为内标,经乙腈-甲醇沉淀蛋白后,采用ACE 5 C4 column(50 mm×2.1 mm,2.5 μm)色谱柱,以0.1%甲酸水和0.1%甲酸乙腈为流动相,进行梯度洗脱分离,流速0.7 mL·min-1,进样量10 μL;采用电喷雾离子源(ESI),正离子扫描方式,MRM扫描,分别以m/z 445.15→270.10和m/z 472.40→436.40作为化合物GY005 和内标(特非那定)的质谱检测条件.大鼠灌服2 mg·kg-1化合物GY005后,不同时间点取样测定其血浆浓度,计算药代动力学参数.雌雄SD大鼠单次静脉注射2 mg·kg-1的受试品后,化合物GY005在雄性大鼠体内的暴露量(AUClast)为(228±44)h·ng·mL-1,消除半衰期(T1/2)为(0.30±0.01)h,清除率(CL)为(149±29)mL·min-1·kg-1.化合物GY005在雌性大鼠体内的暴露量(AUClast)为(215±158)h·ng·mL-1,消除半衰期(T1/2)为(0.32±0.03)h,清除率(CL)为(226±162)mL·min-1·kg-1.雌雄间暴露水平相当,没有显著性差异.这个方法具有简便、灵敏、快捷,适用于化合物GY005的药代动力学研究.
Abstract
To establish a method LC-MS/MS for the determination of the pyrimidine nucleoside compound GY005 concentration in rat plasma and to study its pharmacokinetics in rats.Terfenadine was used as the internal standard.After the protein was precipitated by acetonitrile-methanol,the plasma samples were separated on the ACE 5 C4(50 mm×2.1 mm,2.5μ m)chromatographic column through gradient elution by water(0.1%formic acid)-acetonitrile(0.1%formic acid)as the mobile phase.The flow rate was 0.7 mL·min-1 and sample volume was 10 μL.Then the analytes were detected by electrospray ionization(ESI)source in with positive ion scanning.The detection conditions of GY005 and internal standard(terfenadine)by mass spectrometry were m/z 445.15 → 270.10 and m/z 472.40 → 436.40,respectively.After the rats were given 2 mg·kg-1 GY005 and the plasma concentration of GY005 was detected at different time points.The pharmacokinetic parameters were calculated.After single intravenous injection GY005(2 mg·kg-1)to male and female rats,the main pharmacokinetic parameters were as follows:male rats:AUClast was(228±44)h·ng·mL-1,T1/2 was(0.30±0.01)h,CL was(149±29)mL·min·kg-1;female rats:AUClast was(215±158)h·ng·mL-1,T1/2 was(0.30±0.03)h,CL was(226±162)mL·min-1·kg-1.There is no significant difference in exposure levels between males and females.This method is simple,sensitive and rapid for pharmacokinetic study of GY005.
基金项目
国家自然科学基金(21424034)
河南省科技创新杰出青年项目(094100510019)
河南省科学院基本科研费项目(220602011)
河南省科学院基本科研费项目(230602007)
河南省科技攻关计划(232102310380)
河南省理化分析测试工程技术中心运行费项目(231002007)
NETL
NSTL
万方数据