基于高效液相-质谱联用法对小鼠血液中裕贝甲素的药代动力学研究  

A study on the pharmacokinetics of yubeinine in mouse blood by UPLC-MS/MS

作　　者：陈迪[1] 鲍曦 江夏娟 王贤亲 CHEN Di;BAO Xi;JIANG Xia-juan;WANG Xian-qin(Department of Pharmacy,Second Affiliated Hospital of Wenzhou Medical University,Wenzhou,Zhejiang 325000,China;不详)

机构地区：[1]温州医科大学附属第二医院药学部,浙江温州325000 [2]温州医科大学附属第一医院药学部,浙江温州325000 [3]温州医科大学分析测试中心,浙江温州325035

出　　处：《中国卫生检验杂志》2020年第20期2464-2467,共4页Chinese Journal of Health Laboratory Technology

摘　　要：目的建立高效液相-质谱联用法(UPLC-MS/MS)测定小鼠血液中裕贝甲素的含量,并对小鼠裕贝甲素舌下注射或灌胃后的药代动力学进行研究。方法采用乙腈沉淀法去除血液样品中的蛋白,以去氢鄂贝定碱为内标,采用UPLC BEH (2.1 mm×50 mm,1.7μm)柱为分离柱,柱温为30℃,流动相由乙腈和0.1%甲酸组成,梯度洗脱流速为0.4 ml/min。MRM模式对裕贝甲素m/z 430.2→412.2和内标m/z 414.4→91.1进行定量分析。采用DAS 2.0软件非房室模式计算相关药动学参数。结果在1 ng/ml^1 000 ng/ml浓度范围内,小鼠血液中裕贝甲素线性良好(r>0.995),最低定量下限为1 ng/ml。小鼠血液中裕贝甲素日内精密度RSD<10%,日间精密度RSD<14%,回收率为62.4%~66.4%,基质效应在91.8%~110.1%。结论该方法灵敏、快速、选择性好,可应用于裕贝甲素小鼠舌下与灌胃后的药代动力学研究。Objective In this study,a precise,rapid and accurate UPLC-MS/MS method for the quantitication of yubeinine in mouse blood was developed,and the pharmacokinetics of yubeinine was studied for the first time after intravenous and oral administration.Methods The protein in blood was precipitated with acetonitrile and then yubeinine was separated with UPLC BEH( 2.1 mm × 50 mm,1.7 μm) column at 30 ℃,using ebeiedinone as the internal standard( IS).The mobile phase consisted of acetonitrile-0.1% formic acid,with a flow rate at 0.4 ml/min.MRM modes of m/z 430.2→412.2 for yubeinine and m/z 414.4→91.1 for IS were utilized to conduct quantitative analysis.The main pharmacokinetic parameters were studied by DAS2.1 software( China Medical University).Results The linear range of the method was 1 ng/ml-1 000 ng/ml with r>0.995,and LOQ was 1 ng/ml.The intra-and inter-day RSDs were<10% and RSD<14%,respectively.The recoveries ranged from 62.4% to 66.4%,while the matrix effects were between 91.8% and 110.1%.Conclusion The method is sensitive,rapid and selective,and can be used to study the pharmacokinetics of yubeixin sublingual and intragastric administration in mice.

关 键 词：裕贝甲素 药代动力学 生物利用度 大鼠 高效液相-质谱联用法 

分 类 号：O657.[理学—分析化学]