文章摘要
沈叶,黄烽如,李娜娜,房秋晨,钱燕宁,孙鲁宁,王永庆.LC-MS/MS法同时测定人血浆中咪达唑仑和 1-羟基咪达唑仑的浓度[J].药学与临床研究,2021,29(4):251~255
LC-MS/MS法同时测定人血浆中咪达唑仑和 1-羟基咪达唑仑的浓度
Simultaneous Determination of Midazolam and 1-Hydroxymidazolam in Human Plasma by LC-MS / MS
投稿时间:2021-03-05  修订日期:2021-08-15
DOI:
中文关键词: 咪达唑仑  1-羟基咪达唑仑  血浆  LC-MS/MS法
英文关键词: Midazolam  1-hydroxymidazolam  Plasma  LC-MS/MS
基金项目:南京医科大学第一附属医院(江苏省人民医院)优秀中青年人才支持计划;国家自然科学基金(81503160)
作者单位E-mail
沈叶 徐州医科大学江苏省新药研究与临床药学重点实验室 13053261676@163.com 
黄烽如 南京医科大学第一附属医院药学部  
李娜娜 南京医科大学第一附属医院麻醉与围术期医学科  
房秋晨 南京医科大学第一附属医院药学部  
钱燕宁 南京医科大学第一附属医院麻醉与围术期医学科  
孙鲁宁 南京医科大学第一附属医院药学部  
王永庆 南京医科大学第一附属医院药学部 wyqjsph@163.com 
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中文摘要:
      目的:建立同时测定人血浆样本中咪达唑仑和1-羟基咪达唑仑浓度的LC-MS/MS方法。方法:以d4-咪达唑仑为内标,血浆样本加入含内标的乙腈处理后进样分析。色谱柱为Kinetex C18(2.1 mm × 50 mm,2.6 μm),流动相为乙腈-1 mmol·L-1甲酸铵溶液(含0.1%甲酸),梯度洗脱,流速为0.3 mL·min-1,进样量为3.0 μL。质谱条件采用电喷雾正离子源,扫描方式为多重反应监测,用于定量分析的检测离子分别为m/z 325.9→291.0(咪达唑仑)、m/z 342.0→324.1(1-羟基咪达唑仑)、m/z 329.9→295.0(d4-咪达唑仑)。结果:咪达唑仑和1-羟基咪达唑仑分别在0.300~200 ng·mL-1和0.150~100 ng·mL-1线性关系良好,定量下限分别为0.300 ng·mL-1和0.150 ng·mL-1,批内和批间精密度均小于15%,准确度在-4.7%~9.9%,基质效应为95.5%~101.4%,提取回收率为100.6%~102.4%。血浆样本室温放置12 h、3次冻融循环及-40 ℃冰冻12个月稳定性良好,待测溶液进样器放置24 h稳定。结论:本研究建立的分析方法灵敏、准确,样本前处理简便、快捷,可用于人血浆样本中咪达唑仑和1-羟基咪达唑仑浓度的测定。
英文摘要:
      Objective: To establish an LC-MS/MS method for the simultaneous determination of midazolam and 1-hydroxymidazolam in human plasma samples. Methods: Midazolam-d4 was used as the internal standard (IS). Plasma samples were analyzed after treatment with acetonitrile containing IS. Chromatographic separation was performed on a Kinetex C18 column (2.1 mm × 50 mm, 2.6 μm). Mobile phase consisted of acetonitrile and 1 mmol·L-1 ammonium formate solution (containing 0.1% formic acid). A gradient elution was applied with a flow rate of 0.3 mL·min-1. API 4000 detector coupled with HPLC LC-1290 was operated in a positive mode by multiple reaction monitoring. Ion transitions at m/z 325.9→291.0 for midazolam, m/z 342.0→324.1 for 1-hydroxymidazolam and m/z 329.9→295.0 for midazolam-d4 were selected for the HPLC-MS/MS analysis, respectively. Results: Midazolam and 1-hydroxymidazolam were linear within the range of 0.300-200 ng·mL-1 and 0.150-100 ng·mL-1, respectively. The intra-and inter-run precisions were within 15.0%, and the accuracies were in the range of -4.7%-9.9%. The matrix effects were 95.5%-101.4%, and the recoveries were 100.6%-102.4%. The plasma samples were stable at 25 ℃ for 12 hours, within freezing-thawing 3 circles and at -40 ℃ for 12 months, and the supernatants after preparation were stable at 10 ℃ for 24 hours. Conclusion: In this study, a sensitive, accurate and convenient method for simultaneous determination of midazolam and 1-hydroxymidazolam in human plasma was established, which could provide a reliable method for clinical rational use of midazolam.
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