Page 69 - 《中国药房》2023年16期

·药物与临床·

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

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余恒毅 ，徐艳娇，向 东，刘 璐，李喜平，刘 东，贡雪芃（华中科技大学同济医学院附属同济医院药学部，
武汉 430030）

中图分类号 R917；R971+.6 文献标志码 A 文章编号 1001-0408（2023）16-1979-05
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，V/V）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-C18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，V/V/V）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m/z 251.2→144.1（拉
考沙胺）、m/z 350.2→219.2（吡仑帕奈）、m/z 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（r＞0.99）、0.037 5～3.75 ng/mL（r＞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。
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

Simultaneous determination of lacosamide and perampanel concentration in human plasma by LC-MS/MS
YU Hengyi，XU Yanjiao，XIANG Dong，LIU Lu，LI Xiping，LIU Dong，GONG Xuepeng（Dept. of Pharmacy，
Tongji Hospital of Tongji Medical College， Huazhong University of Science and Technology， Wuhan 430030，
China）

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，V/V）， and the plasma minimum
concentrations were obtained by dilution of multiple. The determination was performed on Welch Ultimate XB-C18 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， V/V/V） 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 m/z 251.2→
144.1， m/z 350.2→219.2 and m/z 327.2→270.0， respectively. RESULTS The linear ranges of lacosamide and perampanel were
0.001 25-0.125 μg/mL（r＞0.99）， 0.037 5-3.75 ng/mL （r＞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
Δ 基金项目 湖北省自然科学基金项目（No.2022CFB142） monitoring of lacosamide and perampanel.
＊第一作者 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 KEYWORDS lacosamide； perampanel； plasma concentration；
# 通信作者 副主任药师，博士。研究方向：治疗药物监测与个体 therapeutic drug monitoring； LC-MS/MS
化给药。E-mail：g1020947167@163.com

中国药房 2023年第34卷第16期 China Pharmacy 2023 Vol. 34 No. 16 · 1979 ·