LC-MS/MS法同时测定拉考沙胺和吡仑帕奈的血浆药物浓度

余恒毅; 徐艳娇; 向东; 刘璐; 李喜平; 刘东; 贡雪芃

doi:10.6039/j.issn.1001-0408.2023.16.11

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LC-MS/MS法同时测定拉考沙胺和吡仑帕奈的血浆药物浓度

药物与临床 | 更新时间：2023-08-24

- LC-MS/MS法同时测定拉考沙胺和吡仑帕奈的血浆药物浓度
- Simultaneous determination of lacosamide and perampanel concentration in human plasma by LC-MS/MS
- 中国药房 2023年34卷第16期页码：1979-1983
- 作者机构：
  
  华中科技大学同济医学院附属同济医院药学部，武汉　430030
- 作者简介：
  
  副主任药师，博士。研究方向：治疗药物监测与个体化给药。E-mail：yuhengyichina@163.com
  副主任药师，博士。研究方向：治疗药物监测与个体化给药。E-mail：g1020947167@163.com
- 基金信息：
  
  湖北省自然科学基金项目(2022CFB142)
- DOI：10.6039/j.issn.1001-0408.2023.16.11
  中图分类号： R917;R971+.6
- 纸质出版日期：2023-08-30，
  
  收稿日期：2023-01-29，
  
  修回日期：2023-07-12，
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余恒毅,徐艳娇,向东等.LC-MS/MS法同时测定拉考沙胺和吡仑帕奈的血浆药物浓度 ^Δ[J].中国药房,2023,34(16):1979-1983.

YU Hengyi,XU Yanjiao,XIANG Dong,et al.Simultaneous determination of lacosamide and perampanel concentration in human plasma by LC-MS/MS[J].ZHONGGUO YAOFANG,2023,34(16):1979-1983.
余恒毅,徐艳娇,向东等.LC-MS/MS法同时测定拉考沙胺和吡仑帕奈的血浆药物浓度 ^Δ[J].中国药房,2023,34(16):1979-1983. DOI： 10.6039/j.issn.1001-0408.2023.16.11.

YU Hengyi,XU Yanjiao,XIANG Dong,et al.Simultaneous determination of lacosamide and perampanel concentration in human plasma by LC-MS/MS[J].ZHONGGUO YAOFANG,2023,34(16):1979-1983. DOI： 10.6039/j.issn.1001-0408.2023.16.11.

摘要

目的

建立同时测定人血浆中2种第三代抗癫痫药拉考沙胺和吡仑帕奈血浆药物浓度的方法并应用于临床。

方法

10例癫痫患者的血浆样品经乙腈沉淀蛋白并以乙腈-水（20∶80，

）稀释后，以氯氮平为内标，采用液相色谱-串联质谱法测定拉考沙胺、吡仑帕奈的质量浓度，再通过稀释倍数换算得血浆药物谷浓度。以Welch Ultimate XB-C

为色谱柱，以10 mmol/L甲酸铵溶液为流动相A、甲醇-乙腈-异丙醇（0.2%甲酸）混合溶液（7∶1.5∶1.5，

）为流动相B进行梯度洗脱，流速为0.4 mL/min，柱温为40 ℃，进样量为5 μL；采用电喷雾离子源以多反应监测模式进行正离子扫描，用于定量分析的离子对分别为

251.2→144.1（拉考沙胺）、

350.2→219.2（吡仑帕奈）、

327.2→270.0（内标）。

结果

拉考沙胺、吡仑帕奈检测质量浓度的线性范围分别为0.001 25～0.125 μg/mL（

＞0.99）、0.037 5～3.75 ng/mL（

＞0.99），定量下限分别为0.001 25 μg/mL、0.037 5 ng/mL；批内、批间精密度，准确度，提取回收率，基质效应，稳定性均符合相关要求。1～5号患者体内拉考沙胺的谷浓度为5.3～12.2 μg/mL，6～10号患者体内吡仑帕奈的谷浓度为208～510 ng/mL。

结论

所建方法操作简便、快速，可用于拉考沙胺和吡仑帕奈的治疗药物监测。

Abstract

OBJECTIVE

To establish a method for simultaneous determination of two third-generation anti-epileptic medicines such as lacosamide and perampanel in human plasma and apply this method in clinical practice.

METHODS

Using clozapine as internal standard， the concentrations of lacosamide and perampanel of plasma samples in 10 epileptic patients were determined by LC-MS/MS after protein precipitation with acetonitrile and dilution with acetonitrile-water （20∶80，

）， and the plasma minimum concentrations were obtained by dilution of multiple. The determination was performed on Welch Ultimate XB-C

column， with mobile phase A consisted of 10 mmol/L ammonium formate and mobile phase B consisted of methanol-acetonitrile-isopropanol （0.2% formic acid） mixed solution （7∶1.5∶1.5，

） for gradient elution at the flow rate of 0.4 mL/min. The column temperature was set at 40 ℃， and the sample size was 5 μL. The electrospray ion source and multi-reaction monitoring mode were used for positive iron scanning. The ion pair used for quantitative analysis of lacosamide， perampanel and internal standard were

251.2→144.1，

350.2→219.2 and

327.2→270.0， respectively.

RESULTS

The linear ranges of lacosamide and perampanel were 0.001 25-0.125 μg/mL（

＞0.99）， 0.037 5-3.75 ng/mL （

＞0.99）； the limits of quantification were 0.001 25 μg/mL and 0.037 5 ng/mL， respectively. The precision and accuracy within and between batches， extraction recovery rate， matrix effect， and stability all met relevant requirements. The minimum concentrations of lacosamide in No.1-5 patients were 5.3-12.2 μg/mL， and the minimum concentrations of perampanel in No.6-10 patients were 208-510 ng/mL， respectively.

CONCLUSIONS

The established method is simple， rapid and suitable for the therapeutic drug monitoring of lacosamide and perampanel.

关键词

拉考沙胺吡仑帕奈血浆药物浓度治疗药物监测液相色谱-串联质谱法

Keywords

perampanelplasma concentrationtherapeutic drug monitoringLC-MS/MS

references

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WANG Y，CHEN Z. An update for epilepsy research and antiepileptic drug development：toward precise circuit therapy[J]. Pharmacol Ther，2019，201：77-93.

渠蕊，陈旭勤，戴园园. 拉考沙胺和吡仑帕奈单药治疗癫痫的研究进展[J]. 癫痫杂志，2021，7（4）：350-354.

国家药品监督管理局. 拉考沙胺片注册信息[EB/OL].（2018-11-21）[2022-07-24]. https：//www.nmpa.gov.cn/datasearch/search-info.html?nmpa=aWQ9MzcwMSZpdGV-tSWQ9ZmY4MDgwODE3YzgzMTJjNDAxN2M5YzU5-MjI0ZTA0NWQ=https://www.nmpa.gov.cn/datasearch/search-info.html?nmpa=aWQ9MzcwMSZpdGV-tSWQ9ZmY4MDgwODE3YzgzMTJjNDAxN2M5YzU5-MjI0ZTA0NWQ=.

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国家药典委员会. 中华人民共和国药典：四部[M]. 2020年版. 北京：中国医药科技出版社，2020：466-472.

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DAI H R，HU Y H，LONG J Y，et al. LC-MS/MS assay for the therapeutic drug monitoring of perampanel in chil-dren with drug-resistant epilepsy[J]. AChrom，2023，35（2）：149-160.

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