Valproic acid (VPA) dosing needs to be individualized for epilepsy patients through therapeutic drug monitoring (TDM). The patients must show up in the clinic at the therapeutic window time to venipuncture sample. Dried plasma spot (DPS) sampling is an alternative way to replace conventional venipuncture sampling. The aim of this study was to develop and validate a DPS‐based liquid chromatography–tandem mass spectrometry (LC–MS/MS) method to monitor VPA in a routine clinical laboratory setting. We compare the DPS with the wet plasma method of clinical samples by LC–MS/MS. The method was linear over the dynamic range of 10–200 μg/ml (covering entire therapeutic range) with a correlation coefficient r² ≥ 0.995. Both the DPS and wet plasma methods were fully validated for the accuracy, precision, recovery, and matrix effect. The analyte stability was examined under conditions mimicking the sample storage, transport, and analysis procedures. A clinical study with epilepsy patients receiving VPA (n = 35) showed that, after correction for hematocrit (HCT), plasma concentrations can be successfully calculated from the DPS quantification results. Passing–Bablok regression coefficients showed no proportional bias between estimated and measured plasma concentrations. Similar agreement was found by Bland–Altman plots. The dried sample could be mailed to the clinical lab to test by regular mail service. So DPS can be used for drug monitoring with self‐sampling strategy at the patient's convenient time and place specially for ambulatory patients not attending a clinic.

中文翻译：

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使用干血浆点取样装置监测丙戊酸的治疗药物

丙戊酸 (VPA) 剂量需要通过治疗药物监测 (TDM) 对癫痫患者进行个体化。患者必须在静脉穿刺样本的治疗窗口时间出现在诊所。干血浆点 (DPS) 采样是替代传统静脉穿刺采样的替代方法。本研究的目的是开发和验证基于 DPS 的液相色谱-串联质谱 (LC-MS/MS) 方法，以在常规临床实验室环境中监测 VPA。我们通过 LC-MS/MS 将 DPS 与临床样品的湿等离子体方法进行了比较。该方法在 10–200 μg/ml（覆盖整个治疗范围）的动态范围内呈线性，相关系数为r ²≥ 0.995。DPS 和湿等离子体方法的准确度、精密度、回收率和基质效应都得到了充分验证。在模拟样品储存、运输和分析程序的条件下检查分析物的稳定性。癫痫患者接受 VPA 的临床研究 ( n= 35) 表明，在校正血细胞比容 (HCT) 后，可以从 DPS 定量结果成功计算血浆浓度。Passing-Bablok 回归系数显示估计和测量的血浆浓度之间没有比例偏差。Bland-Altman 图也发现了类似的一致性。干燥的样本可以通过普通邮件服务邮寄到临床实验室进行测试。因此，DPS 可用于在患者方便的时间和地点采用自采样策略进行药物监测，特别是非门诊患者。