LC／MS／MS测定比格犬血浆中丁螺环酮浓度及其在药代动力学研究中的应用  

Determination of buspirone in beagle plasma by LC/MS/MS and its application in pharmacokinetics

作　　者：崔孟珣[1] 陈燕 李敬来[1] 王晓英[1] 张振清[1] 阮金秀[1] 

机构地区：[1]军事医学科学院毒物药物研究所,北京100850 [2]北京华素制药股份有限公司,北京102488

出　　处：《军事医学科学院院刊》2009年第2期124-127,共4页Bulletin of the Academy of Military Medical Sciences

摘　　要：目的：建立LC／MS／MS测定比格犬血浆中丁螺环酮的方法，并应用于其缓释制剂药代动力学研究。方法：血浆样品经液-液萃取，内标选用曲马多，色谱柱采用Zorbax SB-C18柱（2．1mm×100mm，3．5μm）；流动相为甲醇-水-甲酸（40：60：0．1），流速0．2ml／min；用美国Finnigan公司TSQ Quantum型液相色谱-质谱联用仪器，配有电喷雾离子化电离源（ESI），正离子检测模式，扫描方式为选择反应监测（SRM），用于定量分析的离子反应分别为m／z 386．2→121．97（丁螺环酮）和m／z 264．3→58．0（内标，曲马多）。结果：测定丁螺环酮的线性范围为0．025→7．5μg/L，相关系数为0．99893，提取回收率为72．2％，方法回收率为99．1％，日内日间精密度均小于10．7％，血浆中丁螺环酮的最低定量下限为0．025μg／L。结论：该方法简便、快速、准确，灵敏度高，专一性好，成功应用于丁螺环酮缓释制刺的药代动力学研究。Objective：To develop a sensitive and specific LC/MS/MS method for direct determination of buspirone in heagle dog plasma and to study the pharmacokinetics of its sustained release dosage. Methods： After a single oral dose of 15 mg buspirone to 6 dogs, plasma concentration was determined. Buspirone and tramadol were extracted from plasma using liquid-liquid extraction method, and then separated on a Zorbax SB-C18 column. The mobile phase consisted of methanolwater-formic acid（40： 60：0.1 ）, at a flow-rate of 0.2 ml/min. A Finnigan TSQ Quantum mass spectrometer equipped with electrospray ionization source was used as detector and was operated in the positive ion mode. Selected reaction monitoring （SRM） using the precursor parent to product ion combinations of m/z 386, 2 to 121.97 and m/z 264.3 to 58.0 was performed to quantify buspirone. The pharmacokinetic parameters of buspirone by non-compartment model were analyzed statistically. Results ： The linear calibration curves were obtained in the concentration range of 0. 025 - 7.5 μg/L. Each plasma sample was chromatographed within 5.0 min. The intra- and inter-day relative standard deviation （RSD） was less than 10.7%. Accuracy determined at three concentrations（0. 125, 1.25 and 5.00 μg/L for buspirone） ranged from 96.31% to 103.8%. Conclusion：The method is sensitive and convenient, and suitable for clinical and preclinical investigation on pharmacokinetics of sustained release dosage of buspirone.

关 键 词：丁螺环酮 LC/MS/MS 血药浓度 药代动力学 

分 类 号：R969.1[医药卫生—药理学]