中国新药杂志

LC-MS/MS法检测人血浆中甲基纳曲酮浓度的分析方法及其应用

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马婧怡 ¹^,² , 张丹 ² , 刘曼 ² , 刘会臣 ³

中国新药杂志 | 实验研究 2021,30(5): 447-453

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中国新药杂志 |实验研究 2021 , 30 (5) : 447 -453

LC-MS/MS法检测人血浆中甲基纳曲酮浓度的分析方法及其应用

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马婧怡¹^,², 张丹², 刘曼², 刘会臣³

作者信息

¹国家药品监督管理局药品审评中心，北京　100022

²航天中心医院，北京　100049

³中国医学科学院阜外医院，北京　100037

作者简介:

马婧怡，女，工程师，主要从事临床药理学研究。E-mail：jenny2738@163.com。

刘会臣，男，主任药师，主要从事临床药理学研究。E-mail：huichenliu@163.com。

Determination of methylnaltrexone in human plasma by LC-MS/MS and its application to a pharmacokinetic study in healthy Chinese volunteers

Jing-yi MA¹^,², Dan ZHANG², Man LIU², Hui-chen LIU³

Affiliations

¹Centre for Drug Evaluation, National Medical Products Administration, Beijing 100022, China

²Aerospace Center Hospital, Beijing 100049, China

³Fuwai Hospital, Chinese Academy of Medical Sciences, Beijing 100037, China

出版时间: 2021-03-15

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摘要

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目的：

建立快速、灵敏、可靠的LC-MS/MS法测定人血浆中甲基纳曲酮的浓度。

方法：

采用弱阳离子交换固相萃取柱进行样品预处理，以溴甲基纳曲酮-d3为内标，通过Ultra PFP Propyl柱（100 mm×2.1 mm，5.0 μm）色谱柱进行分离，流动相为20 mmol·L^-1乙酸铵水溶液（含1%甲酸）和乙腈，等度洗脱（15∶85，v/v），流速0.4 mL·min^-1。通过电喷雾电离（ESI），以多反应监测（MRM）模式进行正离子监测，甲基纳曲酮和内标的离子对分别为m/z 356.3→284.2，m/z 359.3→287.1。

结果：

人血浆中甲基纳曲酮在0.1~120 ng·mL^-1范围内线性关系良好（r>0.99），定量下限为0.1 ng·mL^-1；方法批内、批间精密度<7.2%，准确度为94.5%~100.7%；甲基纳曲酮内标归一化的平均基质效应为99.1%，平均提取回收率为81.4%。该方法成功应用于12例健康受试者皮下注射0.075 mg·kg^-1溴甲基纳曲酮注射液的药动学研究。

结论：

本研究建立的LC-MS/MS分析方法灵敏度高、快速且方法重现性好，满足生物分析的法规要求。

关键词

甲基纳曲酮 / LC-MS/MS / 固相萃取 / 药动学

Abstract

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Objective:

To develop a rapid, robust and sensitive liquid chromatography-tandem mass spectrometric (LC-MS/MS) method for the determination of methylnaltrexone in human plasma.

Methods:

The plasma samples were pretreated by filtering using solid-phase extraction (SPE) with a weak cation-exchange cartridge. The filtrate samples were separated on an Ultra PFP Propyl column (100 mm×2.1 mm, 5.0 μm) using 20 mmol·L^-1 ammonium acetate (containing 1% formic acid) in water-acetonitrile (15∶85, v/v) as mobile phase and methylnaltrexone-d3 as the internal standard (IS). The flow rate was set at 0.4 mL·min^-1. Methylnaltrexone and IS were ionized with an ESI source and MRM mode was applied and operated in positive ion mode. The detected ions were m/z 356.3→284.2 and m/z 359.3→287.1, respectively.

Results:

The linear range of the developed method was 0.1~120 ng·mL^-1, with the lower limit of quantification being 0.1 ng·mL^-1. The intra-day and inter-day precisions of the method were less than 7.2% across three validation runs, and the accuracy ranged 94.5%~100.7%. The extraction method using SPE reached a mean recovery of 81.4% for methylnaltrexone, and the mean normalized matrix effect was 99.1%. This method was successfully applied for the pharmacokinetic study of subcutaneous injection of methylnaltrexone bromide in 12 healthy volunteers.

Conclusion:

This LC-MS/MS method is proven sensitive, rapid and reproducible, and meets the regulatory requirements of biological analysis.

Key words

methylnaltrexone / LC-MS/MS / solid-phase extraction (SPE) / pharmacokinetics

引用本文

马婧怡, 张丹, 刘曼, 刘会臣. LC-MS/MS法检测人血浆中甲基纳曲酮浓度的分析方法及其应用. 中国新药杂志, 2021 , 30 (5) : 447 -453 .

Jing-yi MA, Dan ZHANG, Man LIU, Hui-chen LIU. Determination of methylnaltrexone in human plasma by LC-MS/MS and its application to a pharmacokinetic study in healthy Chinese volunteers[J]. Chinese Journal of New Drugs, 2021 , 30 (5) : 447 -453 .

参考文献

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参考文献引证文献

排序方式：

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YUAN CS. Methylnaltrexone mechanisms of action and effects on opioid bowel dysfunction and other opioid adverse effects[J]. Ann Pharmacother, 2007, 41(6): 984-993.

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RUSSELL J, BASS P, GOLDBERG LI, et al. Antagonism of gut, but not central effects of morphine with quaternary narcotic antagonists[J]. Eur J Pharmacol, 1982, 78(3): 255-261.

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KIM C, CHENG R, CORRIGALL WA, et al. Assay for methylnaltrexone in rat-brain regions and serum by high-performance liquid-chromatography with coulometric electrochemical detection[J]. Chromatographia, 1989, 28(7): 359-363.

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U.S. Food and Drug Administration. Relistor (methylnaltrexone bromide) prescibing information[EB/OL]. (2008-04-24). https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/021964s000_ClinPharmR.pdf.

2021年第30卷第5期

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首发时间：2026-10-29
出版时间：2021-03-15

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录用日期：2020-08-10

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¹国家药品监督管理局药品审评中心，北京　100022

²航天中心医院，北京　100049

³中国医学科学院阜外医院，北京　100037

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2种不同金属材料的力学参数

科 Family	属数 Number of genus	种数 Number of species	占总种数比例 Percentage of total species (%)	属 Genus	种数 Number of species	占总种数比例 Percentage of total species (%)
鹅膏菌科Amanitaceae	2	11	5.26	鹅膏菌属 Amanita	10	4.78
小菇科 Mycenaceae	2	12	5.74	丝盖伞属 Inocybe	5	2.39
多孔菌科 Polyporaceae	8	14	6.70	蜡蘑属 Laccaria	5	2.39
红菇科 Russulaceae	3	23	11.00	小皮伞属 Marasmius	6	2.87
				小菇属 Mycena	11	5.26
				光柄菇属 Pluteus	5	2.39
				红菇属 Russula	17	8.13
				栓菌属 Trametes	5	2.39

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