LC-MS/MS法同时测定Beagle犬血浆中乙胺丁醇和异烟肼的质量浓度  

Determination of ethambutol and isoniazid in Beagle dogs plasma by LC-MS /MS

作　　者：李维维[1] 金艺[1] 徐晓敏 王宜美 徐海燕[1] LI Weiwei;JIN Yi;XU Xiaomin;WANG Yimei;XU Haiyan(School of Pharmacy,Shenyang Pharmaceutical University,Shenyang 110016,China)

机构地区：[1]沈阳药科大学药学院,辽宁沈阳110016

出　　处：《沈阳药科大学学报》2020年第9期809-814,840,共7页Journal of Shenyang Pharmaceutical University

摘　　要：目的建立一种灵敏、快速的LC-MS/MS方法测定犬血浆中乙胺丁醇和异烟肼的质量浓度并研究这两种药物在Beagle犬体内的药物动力学。方法以乙胺丁醇-d8作为内标,采用蛋白沉淀法处理血浆样品;使用XBridge Amide色谱柱(50 mm×2.1 mm,3.5μm)进行分离;采用等度洗脱,流动相为乙腈(含体积分数0.3%甲酸)-5 mnmol·L^-1乙酸铵(含体积分数0.3%甲酸溶液)体积比77∶23,流速0.5 mL·min^-1。在多反应离子监测的正离子检测方式下测定。6只健康雄性Beagle犬单次经口给予盐酸乙胺丁醇片250 mg和异烟肼片100 mg,用WinNonlin 8.1软件以非房室模型计算药动学参数。结果犬血浆中乙胺丁醇和异烟肼的质量浓度线性范围分别为12.5~2000μg·L^-1和62.5~10000μg·L^-1,r均大于0.99;方法的日内和日间精密度(CV)不大于9.31%;犬血浆中乙胺丁醇和异烟肼的基质效应的RSD不大于9.17%。结论该方法适用于经口给予盐酸乙胺丁醇片和异烟肼片后Beagle犬体内的药物动力学研究。Objective To develop a sensitive and rapid liquid chromatography-tandem mass spectrometry method for the determination of ethambutol and isoniazid in Beagle plasma,and to study their pharmacokinetics characteristic in Beagle dog plasma.Methods Plasma samples were pretreated by protein precipitation method with acetonitrile.The chromatographic separation was accomplished on XBridge Amide analytical column(50 mm×2.1 mm,3.5μm)using isocratic elution of acetonitrile and 5 mnmol·L^-1 ammonium acetate solution containing 0.3%formic acid,respectively.The plasma concentrations of ethambutol and isoniazid were detected by multiple reaction monitoring.Six healthy male Beagle dogs were given a single oral dose of 250 mg of ethambutol hydrochloride tablets and 100 mg of isoniazid.The pharmacokinetic parameters were calculated using WinNonlin 8.1 software in a non-compartmental model.Results The linear calibration curves of ethambutol and isoniazid in dog plasma ranged from 12.5-2000μg·L^-1 and 62.5^-10000μg·L^-1.The correlation coefficients were all above 0.99.The intra-day and inter-day precision(CV)of the method were both less than 9.31%.The RSD values of the matrix effect of ethambutol and isoniazid in dog plasma were both less than 9.17%.Conclusion This LC-MS/MS method meets the requirements of the guiding principles of biological sample analysis methods,which has been proved to be quick,simple and highly sensitive.It can be successfully applied to the pharmacokinetic studies of oral administration of ethambutol hydrochloride tablets and isoniazid tablets in Beagle dogs.

关 键 词：乙胺丁醇 异烟肼 LC-MS/MS 犬血浆 药物动力学 

分 类 号：R917[医药卫生—药物分析学]