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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
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| 篇名： | 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 |
| TITLE： | Establishment and application of the method for plasma concentration determination of lamotrigine，levetiracetam and perampanel in children with epilepsy |
| 摘要： | 目的 建立同时测定癫痫患儿血浆中拉莫三嗪（LTG）、左乙拉西坦（LEV）和吡仑帕奈（PER）浓度的方法并应用于临床。方法血浆样品经乙腈沉淀蛋白后，以PER-D5为内标，采用超高效液相色谱-串联质谱（UPLC-MS/MS）法检测。色谱柱为ACQUITYUPLCHSST3C18，流动相为含0.1%甲酸的5mmol/L乙酸铵溶液-乙腈（梯度洗脱），流速为0.3mL/min，柱温为40℃，进样量为5μL，分析时间为5min；采用电喷雾离子源，以多反应监测方式进行正离子扫描，用于定量分析的离子对分别为m/z255.9→144.9（LTG）、m/z171.1→126.1（LEV）、m/z350.1→219.0（PER）、m/z354.9→220.2（内标）。采用上述UPLC-MS/MS法测定14例联合用药癫痫患儿血浆中上述药物的稳态谷浓度。结果LTG、LEV、PER检测质量浓度的线性范围分别为0.15～24μg/mL（R2＞0.993）、0.3125～50μg/mL（R2＞0.997）、6.25～1000ng/mL（R2＞0.995），定量下限分别为0.15μg/mL、0.3125μg/mL、6.25ng/mL；3种药物日内、日间精密度试验的RSD均不高于9.83%，准确度（相对误差）为－9.33%～13.72%（n＝6或n＝18）；平均提取回收率为86.4%～97.9%，平均基质效应为86.9%～110.0%（n＝6）；稳定性试验的相对误差绝对值均低于15%。14例患儿体内LTG、LEV、PER的稳态谷浓度分别为（5.64±4.03）μg/mL、（10.67±8.78）μg/mL、（450.20±251.27）ng/mL，谷浓度达标率分别为71.4%、37.5%、84.6%。结论所建UPLC-MS/MS法专属性强、检测速度快，可用于联合用药癫痫患儿的血药浓度监测。 |
| 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. |
| 期刊： | 2026年第37卷第10期 |
| 作者： | 宋文琳；周莹；陈浩然；林子越；李岩；刘杰；金太伟；周旭强 |
| AUTHORS： | SONG Wenlin，ZHOU Ying，CHEN Haoran，LIN Ziyue，LI Yan，LIU Jie，JIN Taiwei，ZHOU Xuqiang |
| 关键字： | 拉莫三嗪；左乙拉西坦；吡仑帕奈；癫痫患儿；治疗药物监测；超高效液相色谱-串联质谱法 |
| KEYWORDS： | lamotrigine； levetiracetam； perampanel； epilepsy； children； therapeutic drug monitoring； UPLC-MS/MS method |
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