Page 101 - 《中国药房》2022年8期

·药物与临床·

人血浆中左乙拉西坦和卡马西平同时测定方法的建立 Δ

2
2
1
1，2 #
史 敏 1，2＊ ，任炳楠 ，吴惠珍 ，刘 平 ，吴 茵 （1.河北医科大学研究生学院，石家庄 050017；2.河北省人民
医院药学部，石家庄 050051）
+
中图分类号 R969.1；R971 .6 文献标志码 A 文章编号 1001-0408（2022）08-0987-05
DOI 10.6039/j.issn.1001-0408.2022.08.14

摘 要 目的 建立同时测定人血浆中左乙拉西坦和卡马西平浓度的方法。方法 血浆样品经甲醇沉淀蛋白后，以卡马西平-D10
为内标，采用高效液相色谱-串联质谱法测定其中左乙拉西坦和卡马西平的浓度。以XBridge BEH C18为色谱柱，以甲醇-0.1％甲
酸溶液为流动相进行梯度洗脱，流速为0.35 mL/min，柱温为40 ℃，进样量为2 μL；离子源为电喷雾离子源，采用多反应监测模式
进行正离子扫描，用于定量分析的离子对分别为 m/z 171.3→126.3（左乙拉西坦）、m/z 237.1→194.1（卡马西平）、m/z 247.1→204.1
（内标）。结果 左乙拉西坦和卡马西平检测质量浓度的线性范围分别为0.5～50、0.2～20 μg/mL（r分别为0.997 3、0.998 5），定量下
限分别为 0.5、0.2 μg/mL；日内、日间 RSD 均不高于 10.00％，日内、日间 RE 均在±4.00％之内，平均提取回收率为 95.60％～
105.00％，平均内标校正基质因子为98.40％～110.00％，稳定性试验的RSD均不高于5.60％。采用该法测得22例患者血浆中左
乙拉西坦、卡马西平的浓度分别为3.36～40.90、3.64～9.93 µg/mL。结论 所建同时测定人血浆中左乙拉西坦、卡马西平浓度的高
效液相色谱-串联质谱法快速、灵敏、准确、稳定，可用于癫痫患者血药浓度监测和药动学研究。
关键词 左乙拉西坦；卡马西平；血药浓度；高效液相色谱-串联质谱法

Establishment of the method for simultaneous determination of levetiracetam and carbamazepine in
human plasma
SHI Min ，REN Bingnan ，WU Huizhen ，LIU Ping ，WU Yin （1. Graduate School，Hebei Medical University，
1
2
1，2
1，2
2
Shijiazhuang 050017，China；2. Dept. of Pharmacy，Hebei General Hospital，Shijiazhuang 050051，China）
ABSTRACT OBJECTIVE To establish the method for simultaneous determination of levetiracetam and carbamazepine
concentrations in human plasma. METHODS After plasma samples were precipitated with methanol，using carbamazepine-D10 as
the internal standard， the concentrations of levetiracetam and carbamazepine were determined by high performance liquid
chromatography-tandem mass spectrometry（HPLC-MS/MS）. The determination was performed on XBridge BEH C18 column with
methanol-0.1％ formic acid as mobile phase（gradient elution）at the flow rate of 0.35 mL/min. The column temperature was set at
40℃ ，and sample size was 2 μ L. With electrospray ion source，a multiple reaction monitoring mode was used for positive ion
scanning；the detected ion pairs for quantitative analysis were m/z 171.3→126.3（levetiracetam），m/z 237.1→194.1（carbamazepine），
247.1→204.1（internal standard）. RESULTS The linear range of the concentrations of levetiracetam and carbamazepine were 0.5-50
and 0.2-20 μg/mL（r＝0.997 3 and 0.998 5），respectively；the lower quantitative limits were 0.5 and 0.2 μg/mL，respectively.
RSDs of intra-day and inter-day were all no more than 10.00％. RE of intra-day and inter-day were within ±4.00％；the average
extraction recoveries rate were 95.60％-105.00％；the average internal standard correction matrix factors were 98.40％-110.00％；
RSDs of stability tests were all not higher than 5.60％. The concentrations of levetiracetam and carbamazepine in the plasma of 22
patients measured by this method were 3.36-40.90 and 3.64-9.93 μg/mL，respectively. CONCLUSIONS The established method for
determining the concentration of levetiracetam and carbamazepine in human plasma is fast，sensitive，accurate and stable，and can
be used for the monitoring of plasma concentration and
Δ 基金项目：中国博士后科学基金面上资助项目（No.2018M641-
pharmacokinetic study in epilepsy patients.
609）
＊硕士研究生。研究方向：临床药学。E-mail：shimin140603@ KEYWORDS levetiracetam；carbamazepine；plasma concen-
163.com tration；high performance liquid chromatography-tandem mass
# 通信作者：副主任药师，硕士生导师，博士。研究方向：临床药 spectrometry
学。E-mail：wuyin82@163.com

中国药房 2022年第33卷第8期 China Pharmacy 2022 Vol. 33 No. 8 ·987 ·