Department of Pharmacy, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang, Liaoning Province, China.
Biomed Chromatogr. 2021 Jul;35(7):e5090. doi: 10.1002/bmc.5090. Epub 2021 Mar 8.
With the purpose of carrying out therapeutic drug monitoring (TDM) of nine antiepileptic drugs simultaneously in the clinic, a UPLC-MS/MS assay method was developed and validated. Separation of antiepileptic drugs and internal standard (naproxen and diazepam) was performed on an Agilent Eclipse XDB-C column (50.0 × 2.1 mm, 1.7 μm) using water and acetonitrile as mobile phase for gradient elution. Polarity switch ionization mode (positive-negative-positive) was performed in a total run time of 3.0 min. The method validation was conducted based on bioanalytical method validation guidance, including specificity, calibration curve, precision, accuracy, recovery, matrix effect, stability and dilution integrity, and all of the results satisfied the requirements. Consequently, the proposed method was applied to the TDM of nine antiepileptic drugs and was proved to be sensitive, reliable and specific to determine antiepileptic drugs in human plasma simultaneously. Meanwhile, the TDM results showed that the plasma drug concentration of many patients was not within the effective therapeutic range, especially those taking topiramate, oxcarbazepine and levetiracetam, which was of great guiding significance to rational drug use and timely adjustment of the treatment plan. Therefore, individualized therapy based on advanced analytical methods and TDM theory is of great practical significance.
为了在临床中同时进行九种抗癫痫药物的治疗药物监测（TDM），开发并验证了一种 UPLC-MS/MS 测定方法。采用 Agilent Eclipse XDB-C 柱（50.0×2.1mm，1.7μm），以水和乙腈为流动相进行梯度洗脱，对癫痫药物和内标（萘普生和地西泮）进行分离。在总运行时间为 3.0 分钟的时间内采用极性切换电离模式（正-负-正）。方法验证基于生物分析方法验证指南进行，包括专属性、校准曲线、精密度、准确度、回收率、基质效应、稳定性和稀释完整性，所有结果均符合要求。因此，该方法已应用于九种抗癫痫药物的 TDM，并被证明能够灵敏、可靠和专一地同时测定人血浆中的抗癫痫药物。同时，TDM 结果表明，许多患者的血浆药物浓度不在有效治疗范围内，尤其是服用托吡酯、奥卡西平和左乙拉西坦的患者，这对合理用药和及时调整治疗方案具有重要指导意义。因此，基于先进分析方法和 TDM 理论的个体化治疗具有重要的实际意义。
