Establishment and application of the method for plasma concentration determination of lamotrigine，levetiracetam and perampanel in children with epilepsy
- VernacularTitle:癫痫患儿血浆中拉莫三嗪、左乙拉西坦和吡仑帕奈浓度测定方法的建立及应用
- Author:
Wenlin SONG
1
;
Ying ZHOU
1
;
Haoran CHEN
2
;
Ziyue LIN
3
;
Yan LI
4
;
Jie LIU
5
;
Taiwei JIN
1
;
Xuqiang ZHOU
6
Author Information
1. Dept. of Pharmacy，Children’s Hospital of Suzhou Wujiang District，Jiangsu Suzhou 215200，China
2. General Office，Children’s Hospital of Suzhou Wujiang District，Jiangsu Suzhou 215200，China
3. School of Pharmacy，Soochow University，Jiangsu Suzhou 215100，China
4. Dept. of Neurology，Children’s Hospital of Soochow University，Jiangsu Suzhou 215008，China
5. Dept. of Reproductive Medicine，the Second Affiliated Hospital of Zhejiang Chinese Medical University，Hangzhou 310005，China
6. Dept. of Clinical Laboratory，Children’s Hospital of Suzhou Wujiang District，Jiangsu Suzhou 215200，China
- Publication Type:Journal Article
- Keywords:
lamotrigine;
levetiracetam;
perampanel;
epilepsy;
children;
therapeutic drug monitoring;
UPLC-MS/MS method
- From:
China Pharmacy
2026;37(10):1313-1317
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE To establish a method for simultaneous determination of plasma concentration of lamotrigine（LTG）， levetiracetam（LEV） and perampanel（PER） in children with epilepsy and apply this method in clinical practice. METHODS Plasma proteins were precipitated with acetonitrile. Using PER-D 5 as internal standard， ultra-high performance liquid chromatography-tandem mass spectrometry （UPLC-MS/MS） method was adopted. The determination was performed on ACQUITY UPLC HSS T3 C 18 column with mobile phase consisted of 0.1% formic acid with 5 mmol/L ammonium acetate-acetonitrile （gradient elution） at the flow rate of 0.3 mL/min. The column temperature was 40 ℃， and sample size was 5 μL. The analysis time was 5 min. The electrospray ionization source and multiple reaction monitoring mode were used for positive ion scanning. The ion pairs used for quantitative analysis of LTG， LEV， PER and internal standard were m / z 255.9→144.9， m / z 171.1→126.1， m / z 350.1→219.0 and m / z 354.9→220.2， respectively. The steady-state trough concentrations of the aforementioned drugs in the plasma of 14 pediatric epilepsy patients receiving combination therapy were determined using the same UPLC-MS/MS method as above. RESULTS The linear ranges of LTG， LEV and PER were 0.15-24 μg/mL （ R 2 ＞0.993）， 0.312 5-50 μg/mL （ R 2 ＞0.997） and 6.25-1 000 ng/mL （ R 2 ＞0.997）， respectively. The lower limits of quantification were 0.15 μg/mL， 0.312 5 μg/mL and 6.25 ng/mL， respectively. RSDs of intraday and interday precision tests of the three drugs were no more than 9.83%， and the accuracies （relative errors） were between －9.33% and 13.72%（ n ＝6 or n ＝18）； the average extraction recovery rates were 86.4%-97.9%， and the average matrix effects were 86.9%-110.0% （ n ＝6）. The absolute values of the relative errors in the stability tests were all below 15%. The steady-state trough concentrations of LTG， LEV and PER were （5.64±4.03）μg/mL， （10.67±8.78）μg/mL and（450.20±251.27）ng/mL， respectively； the rates of achieving target trough concentrations were 71.4%， 37.5% and 84.6%， respectively. CONCLUSIONS The established UPLC-MS/MS method is specific， rapid and suitable for the plasma concentration monitoring in epileptic children receiving combination therapy.
