超高效液相色谱串联质谱法测定Beagle犬血浆中米安色林的质量浓度及其在药代动力学研究中的应用  

Determination of mianserin in Beagle dogs plasma by UPLC-MS and its application in pharmacokinetic study

作　　者：何悦 王亚楠 朱晓慧 张天姣 金梓杰 孙璐[1] HE Yue;WANG Yanan;ZHU Xiaohui;ZHANG Tianjiao;JIN Zijie;SUN Lu(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》2025年第4期358-364,共7页Journal of Shenyang Pharmaceutical University

摘　　要：目的建立了快速灵敏的超高效液相色谱串联质谱法测定Beagle犬血浆中米安色林的质量浓度,并将其用于草酸米安色林片和盐酸米安色林片在Beagle犬体内的生物等效性研究。方法使用乙腈沉淀蛋白法处理血浆样品,以米安色林-d_(3)为内标物,采用ACQUITY UPLC BEH C_(18)(50 mm×2.1 mm,1.7μm)色谱柱,流动相为甲醇-水(含体积分数0.01%NH_(3)·H_(2)O,pH=8.4),梯度洗脱分离,流速为0.4 mL·min^(-1)。质谱检测使用ESI源正离子模式。采用双周期自身交叉对照试验设计,使用DAS 3.0软件以非房室模型进行药动学参数计算和生物等效性比较。结果Beagle犬血浆中米安色林质量浓度在0.50~100 ng·mL^(-1)范围内线性关系良好(r≥0.99),日内和日间精密度RSD均不大于7.7%,提取回收率在99.2%~101.6%内,基质效应在98.7%~108.3%内。结论该方法符合生物样品分析方法的相关规定,可用于Beagle犬血浆中米安色林质量浓度的测定。受试制剂草酸米安色林片和参比制剂盐酸米安色林片在Beagle犬体内生物等效。Objective To develop a method for the determination of mianserin in Beagle dogs plasma by ultra-high performance liquid chromatography tandem mass spectrometry and to study the pharmacokinetics profile of mianserin oxalate tablets and mianserin hydrochloride in Beagle dogs.Methods The plasma samples were pretreated by protein precipitation with acetonitrile,using mianserin-d_(3) as the internal standard.Chromatographic separation was performed on an ACQUITY UPLC BEH C_(18) column(50 mm×2.1 mm,1.7 μm) using a gradient elution with a mobile phase consisting of methanol(A) and water containing 0.01% NH_3·H_2O(B).The detection was carried out by Waters Xevo G2 QTOF equipped with electrospray ionization source in positive ion mode.Results The calibration curves of mianserin in Beagle dogs plasma showed good linearity over the concentration ranges of 0.50-100 ng·mL~(-1) respectively.The inter-day and intra-day precisions were lower than 7.7% for all analytes.The extraction recovery was between 99.2% and 101.6%.The matrix effect was between 98.7% and 108.3%.Conclusion The method was already confirmed by the guidelines on bioanalytical method validation and was suitable for pharmacokinetic study of mianserin in Beagle dogs.The results showed that the two kinds of mianserin tablets were bioequivalent in Beagle dogs.

关 键 词：米安色林 超高液相色谱串联质谱法 药代动力学 生物等效性 

分 类 号：R917[医药卫生—药物分析学]