建立一种 UPLC-MS/MS 法，并用氘代内标同时测定 13 种抗癫痫药物。

Development of a UPLC-MS/MS Method to Simultaneously Measure 13 Antiepileptic Drugs with Deuterated Internal Standards.

出版信息

Clin Lab. 2024 Sep 1;70(9). doi: 10.7754/Clin.Lab.2024.240206.

DOI:10.7754/Clin.Lab.2024.240206

Abstract

BACKGROUND

The goal of this study was to develop and validate a UPLC-MS/MS method for simultaneous mea-surement of 13 AEDs, including carbamazepine, oxcarbazepine, lamotrigine, levetiracetam, topiramate, primidone, zonisamide, gabapentin, lacosamide, perampanel, pregabalin, rufinamide, and vigabatrin, in whole blood samples.

METHODS

A UPLC-MS/MS method for simultaneous determination of 13 AEDs in whole blood was developed, and validation was conducted for accuracy, precision, limit of quantification (LOQ), matrix effect, and stability. Our method was compared to two different hospitals using UPLC-MS/MS.

RESULTS

All AEDs exhibited linearity across the AMR (analytical measurement range), with R2 values ranging from 0.994 to 1.000. The imprecision and inaccuracy for low and high quality control (QC) levels were within an acceptable range, with the coefficient of variation (CV) < 15%. The LOQ was 0.62 µg/mL for carbamazepine, 1.61 µg/mL for oxcarbazepine, 1.30 µg/mL for lamotrigine, 13.20 µg/mL for levetiracetam, 1.26 µg/mL for topira-mate, 1.01 µg/mL for primidone, 1.59 µg/mL for zonisamide, 1.09 µg/mL for lacosamide, 1.61 µg/mL for gabapentin, 0.50 µg/mL for pregabalin, 0.07 ng/mL for perampanel, 3.00 µg/mL for rufinamide, and 2.06 µg/mL for vigabatrin. All AEDs demonstrated acceptable assay parameters for carryover, stability, and matrix effects. Moreover, the assay showed satisfactory results compared to two different hospitals with a bias of less than 15%.

CONCLUSIONS

We successfully developed and validated a fast and robust UPLC-MS/MS method for routine therapeutic drug monitoring of thirteen antiepileptic drugs simultaneously.

摘要

背景

本研究旨在建立并验证一种可同时测定全血中 13 种抗癫痫药物（AEDs）浓度的 UPLC-MS/MS 方法，包括卡马西平、奥卡西平、拉莫三嗪、左乙拉西坦、托吡酯、苯妥英钠、唑尼沙胺、加巴喷丁、拉科酰胺、普瑞巴林、鲁非酰胺、丙戊酸和氨己烯酸。

方法

建立了一种可同时测定全血中 13 种 AEDs 浓度的 UPLC-MS/MS 方法，并对其准确性、精密度、定量下限（LOQ）、基质效应和稳定性进行了验证。本方法与另外两家医院使用的 UPLC-MS/MS 方法进行了比较。

结果

所有 AEDs 的线性范围均符合分析测量范围（AMR），R2 值均在 0.994 至 1.000 之间。低、高浓度质控（QC）的精密度和准确度均在可接受范围内，变异系数（CV）＜15%。卡马西平、奥卡西平、拉莫三嗪、左乙拉西坦、托吡酯、苯妥英钠、唑尼沙胺、拉科酰胺、加巴喷丁、普瑞巴林、鲁非酰胺、丙戊酸和氨己烯酸的 LOQ 分别为 0.62µg/mL、1.61µg/mL、1.30µg/mL、13.20µg/mL、1.26µg/mL、1.01µg/mL、1.59µg/mL、1.09µg/mL、1.61µg/mL、0.50µg/mL、0.07ng/mL、3.00µg/mL 和 2.06µg/mL。所有 AEDs 的方法学参数均显示出可接受的前处理、稳定性和基质效应。此外，与另外两家医院相比，本方法的偏差小于 15%，具有良好的应用效果。