超高效液相色谱-串联质谱法检测大鼠血浆中去氢钩藤碱及其药动学研究  

Determination of corynoxeine and its pharmacokinetics in rat plasma by ultra-high performance liquid chromatography-tandem mass spectrometry

作　　者：林正锋[1] 任可 陈思远 金玥 鲍仕慧[1] 王贤亲 LIN Zheng-feng;REN Ke;CHEN Si-yuan;JIN Yue;BAO Shi-hui;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]宁波市鄞州第二医院,浙江宁波315100 [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12期1409-1411,1415,共4页Chinese Journal of Health Laboratory Technology

基　　金：温州市公益性科技计划项目(Y20170699);鄞州区2018年度第二批农社类科技项目(23)。

摘　　要：目的建立超高效液相色谱-串联质谱法(UPLC-MS/MS)测定大鼠血浆中去氢钩藤碱含量的方法,并将其用于去氢钩藤碱的药代动力学研究。方法地西泮作为内标物,使用UPLC BEH C18柱(2.1 mm×50 mm,1.7μm)作为分离柱,0.1%甲酸-乙腈溶液作为流动相梯度洗脱,0.4 ml/min的流速,用乙腈沉淀法去除蛋白质处理的大鼠血浆样品,采用电喷雾离子源(ESI)的正离子和MRM模型对去氢钩藤碱进行定量分析,去氢钩藤碱m/z 383.2→159.9和内标m/z 285.1→193.3。结果在1 ng/ml^400 ng/ml内,该方法线性良好(r>0.995),定量限为1 ng/ml。准确度在97.0%~105.1%,日内精密度(RSD)<13%,日间精密度(RSD)<14%,回收率高于94.5%,基质效应在95.9%~101.5%。结论该方法灵敏、快速、选择性好,可应用于大鼠去氢钩藤碱药动学研究。主要药代动力学参数用非房室模型拟合,舌下给药时大鼠代谢较快。Objective To establish a ultra-high performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)method for the determination of corynoxeine in rat plasma,and to study the pharmacokinetics of corynoxeine.Methods Diazepam was used as internal standard,a UPLC BEH C18 column(2.1 mm×50 mm,1.7μm)was used for chromatographic separation with the mobile phase consisted of acetonitrile and 0.1%formic acid by gradient elution,the flow rate was set at 0.4 ml/min.Proteins from rat plasma were removed by acetonitrile precipitation.Multiple reaction monitoring(MRM)mode was used for quantitative determination of corynoxeine in electrospray(ESI)positive interface,m/z 383.2→159.9 for corynoxeine and m/z 285.1→193.3 for internal standard.Results In the concentration of 1 ng/ml-400 ng/ml,the calibration curve was good linear(r>0.995),and the lower limit of quantification was 1.0 ng/ml.The intra-day precision was less than 13%,the inter-day precision was less than 14%,the accuracy ranged from 97.0%to 105.1%,the recovery was higher than 94.5%,and the matrix effect was within 95.9%-101.5%.Conclusion The UPLC-MS/MS method was sensitive,rapid and selective,and could be applied to the pharmacokinetic study of corynoxeine in rats.The non-compartmental model fitted the main pharmacokinetic parameters,and the rats were metabolized fast after intravenous administration.

关 键 词：超高效液相色谱-串联质谱法 去氢钩藤碱 药代动力学 

分 类 号：O657.63[理学—分析化学]