JJH201501, a deuterated modification for multi-target antidepressant vortioxetine, is currently in phase I clinical trial. This study aimed to establish a sensitive and rapid UPLC-MS/MS method that was capable of simultaneously detecting JJH201501 and its major metabolite JJH201501-01 quantitatively in human plasma. The pretreatment was achieved by protein precipitation using 4-fold(v:v) acetonitrile with 0.05 ng/mL fluoxetine as internal standard precipitant. For method validation, the method was investigated in terms of the selectivity, inter- and intra-run precision and accuracy, matrix effect, extraction recovery and stability. The total running time was 3 min, and the retention time of JJH201501 and JJH201501-01 was 1.17 min and 1.05 min, respectively. The linear concentration range for JJH201501 and JJH201501-01 was 0.2 to 50 ng/mL and 0.4 to 100 ng/mL, respectively. The results showed that this method was in line with the guidelines for bioanalytical method proposed by FDA. In addition, the method was successfully applied to a plasma pharmacokinetic study of JJH201501 tablets in healthy volunteers which was part of the phase I trial.

JJH201501是一种多靶点抗抑郁药伏替西汀的氘代修饰药物，目前正在进行I期临床试验。本研究旨在建立一种灵敏，快速的UPLC-MS / MS方法，该方法能够同时定量检测人血浆中的JJH201501及其主要代谢物JJH201501-01。预处理是通过使用4倍（v：v）乙腈与0.05 ng / mL氟西汀作为内标沉淀剂进行蛋白质沉淀来实现的。为了进行方法验证，对方法进行了选择性，运行中和运行中的精密度和准确度，基质效应，提取回收率和稳定性方面的研究。总运行时间为3分钟，JJH201501和JJH201501-01的保留时间分别为1.17分钟和1.05分钟。JJH201501和JJH201501-01的线性浓度范围是0.2至50 ng / mL和0。分别为4至100 ng / mL。结果表明该方法符合FDA提出的生物分析方法指南。此外，该方法已成功应用于健康志愿者中JJH201501片剂的血浆药代动力学研究，这是I期试验的一部分。