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刊物信息

期刊名称:药物分析杂志
主管单位:中国科学技术协会
主办单位:中国药学会
承办:中国食品药品检定研究院
主编:金少鸿
地址:北京天坛西里2号
邮政编码:100050
电话:010-67012819,67058427
电子邮箱:ywfx@nicpbp.org.cn
国际标准刊号:ISSN 0254-1793
国内统一刊号:CN 11-2224/R
邮发代号:2-237
 

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LC-MS/MS法测定血浆中马来酸甲麦角新碱及其人体药代动力学研究

Determination of methylergonovine maleate in plasma emd its pharmacokinetic research by LC-MS/MS

作者(英文):
分类号:R917
出版年·卷·期(页码):2018,38 (3):393-398
DOI: 10.16155/j.0254-1793.2017.01.01
-----摘要:-------------------------------------------------------------------------------------------

目的:建立LC-MS/MS法测定人血浆中甲麦角新碱浓度,对肌注0.2 mg马来酸甲麦角新碱注射液后药动学进行研究。方法:以文拉法辛为内标,血浆以NaOH碱化后经乙酸乙酯液液萃取浓缩后进行LC-MS/MS分析。采用高效液相色谱分离系统,色谱柱为CAPCELL CORE C18色谱柱(2.1 mm×100 mm,2.7 μm),流动相为甲醇(0.05%乙酸)-水(5 mmol·L-1乙酸铵,0.05%乙酸)(65:35);采用质谱检测法,多反应监测(MRM)方式监测m/z 340.2→m/z 208.1(甲麦角新碱)和m/z 278.3→m/z 215.1(内标文拉法辛)。结果:建立的LC-MS/MS法在0.025~10 ng·mL-1范围内甲麦角新碱色谱响应与浓度相关性良好,定量限为0.025 ng·mL-1,日内、间精密度RSD均小于7%,准确度在96.7%~112.4%,方法稳定性较好。16名受试者单次肌注0.2 mg马来酸甲麦角新碱注射液后AUC0-8为(12.165±3.345) ng·mL-1·h,AUC0-∞为(12.900±3.800) ng·mL-1·h,Cmax为(4.707±2.541) ng·mL-1tmax为(0.577±0.251) h,t1/2为(1.831±0.457) h,MRT为(2.412±0.246) h,CL为(16.925±5.281) L·h-1Vd为(43.183±14.041) L。结论:该法灵敏准确,简便易行,适用于低剂量甲麦角新碱血药浓度的测定及其药代动力学研究。研究结果显示马来酸甲麦角新碱注射液肌注后吸收较快,0.5 h左右达峰;部分受试者用药后发生恶心、呕吐及头痛等不良事件,但程度均为轻微。

-----英文摘要:---------------------------------------------------------------------------------------

Objective: To develop an LC-MS/MS method for the determination of the concentration of methylergonovine in human plasma and to study its pharmacokinetic parameters after 0.2 mg intramuscular injection of methylergonovine maleate injection.Methods: Venlafaxine was used as an internal standard, plasma was alkalified by NaOH and extracted by ethyl acetate,and then was analyzed by LC-MS/MS.A high performance liquid phase system was used.The mobile phase consisted of CAPCELL CORE C18 column(2.1 mm×100 mm,2.7 μm) with methanol (0.05% acetic acid) -water (5 mmol·L-1 ammonium acetate,0.05% acetic acid) (65:35).m/z 340.2→m/z 208.1 (methylergonovine) and m/z 278.3→m/z 215.1 (internal standard venlafaxine) were monitored by mass spectrometry and multiple reaction monitoring (MRM).Results: The established LC-MS/MS method showed a good correlation with concentration in the range of 0.025-10 ng·mL-1,the limit of quantification was 0.025 ng·mL-1,and RSD of precision was less than 7%,the accuracy was between 96.7%-112.4%,the method had better stability.Mean pharmacokinetic parameters for methylergonovine in 16 volunteers after a single dose of 0.2 mg methylergonovine maleate injection were as follows:AUC0-8(12.165±3.345) ng·mL-1·h,AUC0-∞(12.900±3.800)ng·mL-1·h,Cmax(4.707±2.541)ng·mL-1,tmax(0.577±0.251)h,t1/2 (1.831±0.457)h,MRT(2.412±0.246)h,CL(16.925±5.281)L·h-1,Vd(43.183±14.041)L.Conclusion: The established LC-MS/MS method is simple,sensitive and accurate,which is suitable for the pharmacokinetic study of low dose methylergonovine in human plasma.The results showed that methylergine maleate injection intramuscularly absorbed faster,0.5 h reached peak;Some slight adverse events happened in the study,including nausea,vomiting and headache.

-----参考文献:---------------------------------------------------------------------------------------
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