[1]陈 敏 阳丽梅 罗冬梅 王长连.HPLC-MS/MS法测定人血浆中达比加群的浓度[J].福建医药杂志,2018,40(06):118-122.
　CHEN Min,YANG Limei,LUO Dongmei,et al.Determination of dabigatran in human plasma by HPLC-MS/MS[J].FUJIAN MEDICAL JOURNAL,2018,40(06):118-122.
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HPLC-MS/MS法测定人血浆中达比加群的浓度()
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《福建医药杂志》[ISSN:1002-2600/CN:35-1071/R]

卷:
40
期数:
2018年06期
页码:
118-122
栏目:
基础研究
出版日期:
2018-11-29

文章信息/Info

Title:
Determination of dabigatran in human plasma by HPLC-MS/MS
文章编号:
1002-2600(2018)06-0118-06
作者:
陈 敏 阳丽梅 罗冬梅 王长连1
福建医科大学省立临床医学院 福建省立医院药学部(福州 350001)
Author(s):
CHEN Min;  YANG Limei;  LUO Dongmei;  WANG Changlian.
Department of Pharmacy,Fujian Provincial Hospital,Provincial Clinical Medical College of Fujian Medical University, Fuzhou, Fujian 350001, China
关键词:
达比加群;  HPLC-MS/MS法;  血药浓度
Keywords:
dabigatran;  HPLC-MS/MS;  plasma drug concentration
分类号:
R927.2
文献标志码:
A
摘要:
目的 建立人血浆中达比加群(dabigatran)浓度的HPLC-MS/MS测定法,并对该方法进行方法学验证。方法 血浆样品采用甲醇直接沉淀,选择盐酸苯海拉明作为内标物。色谱柱采用InertSustainC18 HP(3.0 mm×100 mm,3 μm),流动相采用甲醇-5%甲醇水溶液(含有10 mmol/L甲酸铵及0.1%甲酸)进行梯度洗脱。结果 达比加群在10～500 ng/mL范围内呈良好的线性关系(r=0.999 5),定量下限是10 ng/mL; 保留时间是1.8 min,日内、日间精密度(RSD)小于6.75%,准确度在±4.12%以内,基质效应在92.68%～94.37%以内,提取回收率为90.95%～93.83%,血浆内源性物质对分析方法不干扰。结论 本实验建立了一种简单、高效的HPLC-MS/MS法检测人血浆中的达比加群浓度。具有特异性强、专属性高、操作简便、灵敏准确等特点。
Abstract:
Objective To establish a sensitive and specific method for determination of dabigatran in human plasma by HPLC-MS/MS and validated the methods systematically. Methods The plasma samples were precipitated by methanol, and diphenhydramine hydrochloride was selected as the internal standard(IS). The analyte dabigatran and IS were separated on InertSustain C18 HP(3.0×100 mm, 3μm)with mobile phase of methanol-5% methanol aqueous solution(including 10 mmol/L ammonium formate and 0.1% formic acid)in gradient elution. Results The method exhibited a good linearity over the concentration range of 10～500 ng/mL(r=0.999 5). The quantification lower limit of dabigatran was 10 ng /mL, and the retention time was 1.8 min. The values on both the occasion(intra- and inter-day)were all within 6.75%, and the accuracy was within ±4.12%. The matrix effect was within 92.68%-94.37%, and the extraction recoveries were 90.95%-93.83%. There was absent of the interference of endogenous substances in plasma. Conclusion A simple and efficient HPLC-MS/MS method applied to the determination of dabigatran concentration has been established by this study, which is characterized by prominent specificity, simplicity, rapidity, high specificity, sensitivity as well as accuracy.

参考文献/References:

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备注/Memo

备注/Memo:
基金项目:福建省自然科学基金资助项目(2017J01249) 1 福建医科大学药学院
更新日期/Last Update: 2018-11-29