Department of Laboratory Medicine, The First Hospital of Jilin University, Changchun 130061, China.
Department of Breast Disease, The Second Hospital of Jilin University, Changchun 130061, China.
J Pharm Biomed Anal. 2024 Jun 15;243:116099. doi: 10.1016/j.jpba.2024.116099. Epub 2024 Mar 7.
Alternative blood sampling strategy can enhance the application of therapeutic drug monitoring (TDM), then improve precision therapy and medication compliance. In developing nations, alternative sampling strategy that allows self-sampling and room temperature transport is especially important. This study validates the use of dried blood spot (DBS) and dried plasma spot (DPS) sampling along with liquid chromatography-tandem mass spectrometry (LC-MS/MS) for analyzing seven common antiepileptic drugs (AEDs) (phenytoin, lamotrigine, levetiracetam, topiramate, carbamazepine, oxcarbazepine and its active metabolite 10,11-dihydro-10-hydroxy carbamazepine) and evaluates their applicability to clinical practice. Following simple protein precipitation with acetonitrile, the AEDs were separated on a C18 column by gradient elution with a mobile phase consisting of acetonitrile-water-0.1% formic acid at a flow rate of 0.65 mL/min. The method provided linear analysis over the tested concentration ranges, with a total run time of 7 min. Intra- and inter-assay precision for all quality controls were ≤12% with accuracies of 85.9%-113%. The average extraction efficiencies were 69.0%-92.4% for DBS and 65.9%-96.5% for DPS, and no significant matrix effects were observed. The AEDs were stable in all samples for seven days at room temprature and 40°C. There was good correlation between the dry and wet plasma concentrations with greater accuracy for DPS compared to DBS indicating that alternative sampling strategy using DBS and DPS are suitable for monitoring the concentrations of AEDs with satisfied performance and logistical advantages.
替代采血策略可以增强治疗药物监测（TDM）的应用，从而提高精准治疗和用药依从性。在发展中国家，允许自我采血和室温运输的替代采样策略尤为重要。本研究通过使用干血斑（DBS）和干血浆斑（DPS）采样以及液相色谱-串联质谱法（LC-MS/MS）分析七种常见抗癫痫药物（AEDs）（苯妥英、拉莫三嗪、左乙拉西坦、托吡酯、卡马西平、奥卡西平和其活性代谢物 10,11-二氢-10-羟基卡马西平），验证了其应用于临床实践的可行性。在使用乙腈进行简单的蛋白质沉淀后，AEDs 在 C18 柱上通过梯度洗脱分离，流动相由乙腈-水-0.1%甲酸组成，流速为 0.65 mL/min。该方法在测试浓度范围内提供了线性分析，总运行时间为 7 分钟。所有质量控制的内和日间精密度均≤12%，准确度为 85.9%-113%。DBS 的平均提取效率为 69.0%-92.4%，DPS 的平均提取效率为 65.9%-96.5%，且未观察到明显的基质效应。AEDs 在室温下和 40°C 下所有样本中均稳定七天。DPS 与干血浆浓度之间具有良好的相关性，与 DBS 相比具有更高的准确度，表明使用 DBS 和 DPS 的替代采样策略适用于监测 AEDs 的浓度，具有令人满意的性能和后勤优势。
