摘要
目的建立Beagle犬血浆中羟乙基黄芩苷质量浓度的测定方法,研究Beagle犬静脉注射羟乙基黄芩苷后的药动学特征。方法采用LC-MS/MS法。血浆样品经乙酸乙酯萃取,Agilent TC-C18色谱柱分离,盐酸帕罗西汀为内标,流动相为乙腈-甲醇-体积分数1%甲酸溶液(体积比30∶35∶35),电喷雾离子源,以多反应监测模式(multiple reaction monitoring,MRM)进行正离子检测。结果羟乙基黄芩苷线性范围为0.1～500.0 mg·L-1,定量下限为0.1 mg·L-1,日内、日间精密度(relativestandard deviation,RSD)均不大于10.5%,准确度(relative error,RE)为-4.3%～6.0%。Beagle犬静脉注射羟乙基黄芩苷后主要药动学参数:t1/2α为(0.36±0.09)h,t1/2β为(21.0±25.1)h,CL为(0.45±0.13)L.h-.1kg-1,V为(0.46±0.20)L,AUC0-t为(52.2±19.8)mg.h.L-1。结论该方法可用于羟乙基黄芩苷临床前药动学研究。
Objective To establish an LC-MS/MS method to determine 5,6-dihydroxyethyl baicalin and study its pharmacokinetics in Beagle dogs. Methods The plasma containing 5,6-dihydroxyethyl baicalin was extracted by liquid-liquid extraction and then the analyte and internal standard paroxetine were separated on an Agilent TC-C18 column with a mobile phase of acetonitrile-methanol-1% formic acid solution（ V： V： V = 30：35：35）. Detection was performed on a triple quadrupole tandem mass spectrum equipped with electros- pray ionization source by multiple reaction monitoring （MRM） in positive mode. Results The linearity of 5,6-dihydroxyethyl baicalin ranged from 0. 1 to 500.0 mg. L^-1. The lower limit of quantification was 0. 1 mg. L^-1. The intra-and inter-day precision（RSD） was less than 10. 5%, and the accuracy （RE）was be- tween -4.3% and 6.0%. The main pharmacokinetic parameters after an intravenous administration of 5,6- dihydroxyethyl baicalin were as follows： t1/2,was （0. 36 ± 0. 09 ） h, tl1/2βwas （21.0 ± 25.1 ） h, CL was （0. 45 ± 0. 13 ） L. h ^- 1. kg ^- 1, V was （0. 46 ± 0. 20 ） L, AUC0-t was （ 52. 2 ±19. 8 ） mg. h. L^- 1. Conclusions The method can be utilized for the pharmacokinetic study of 5,6-dihydroxyethyl baicalin in Beagle dogs.
出处
《沈阳药科大学学报》
CAS
CSCD
北大核心
2012年第9期708-712,共5页
Journal of Shenyang Pharmaceutical University
基金
国家科技重大专项资助项目(2009ZX09103-056)
