Department of Clinical Laboratory, The First Hospital of Jilin University, Changchun, China.
Department of Breast Disease, The Second Hospital of Jilin University, Changchun, China.
J Mass Spectrom. 2021 Apr;56(4):e4603. doi: 10.1002/jms.4603. Epub 2020 Aug 10.
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 r ≥ 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.
丙戊酸（VPA）的剂量需要通过治疗药物监测（TDM）为癫痫患者进行个体化调整。患者必须在治疗窗时间到诊所进行静脉穿刺取样。干血浆斑（DPS）采样是替代常规静脉穿刺采样的另一种方法。本研究旨在开发和验证一种基于 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。我们将 DPS 与 LC-MS/MS 临床样本的湿血浆方法进行比较。该方法在 10-200μg/ml 的动态范围内呈线性（涵盖整个治疗范围），相关系数 r≥0.995。DPS 和湿血浆方法均经过准确性、精密度、回收率和基质效应的充分验证。在模拟样本储存、运输和分析过程的条件下检查了分析物的稳定性。一项接受 VPA 治疗的癫痫患者的临床研究（n=35）表明，在对红细胞压积（HCT）进行校正后，可以成功地根据 DPS 定量结果计算血浆浓度。通过 Passing-Bablok 回归系数表明，估计的和测量的血浆浓度之间没有比例偏差。Bland-Altman 图也显示了相似的一致性。干燥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 可以用于药物监测，具有患者方便的时间和地点的自我采样策略，特别适用于不参加诊所的门诊患者。
