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采用 LC-MS/MS 对人血清中四类抗抑郁药进行定量分析。

An in-depth analysis of four classes of antidepressants quantification from human serum using LC-MS/MS.

机构信息

Brown University Center for Biomedical Engineering, Providence, RI, USA.

出版信息

Sci Rep. 2023 Feb 6;13(1):2115. doi: 10.1038/s41598-023-29229-0.

DOI:10.1038/s41598-023-29229-0
PMID:36747000
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9902619/
Abstract

Depression is a growing global crisis, with females at a higher rate of diagnosis than males. While the percentage of patients on prescribed antidepressants have tripled over the last two decades, we are still at a crossroad where the discrepancy lies between finding a drug to suit a patient and monitoring the abundance of it in the body to prevent unwanted side effects. Liquid Chromatography tandem mass spectrometry (LC-MS/MS) has garnered the attention of clinicians as a technique to accurately monitor therapeutic drugs in human serum with high specificity and accuracy. This may be a potential solution, but the challenge persists in the realm of sample preparation, where a method is automatable. We have developed and validated an LC-MS/MS-based assay for simultaneous quantification of 4 different classes of commonly prescribed antidepressants in women that is automated using a JANUS G3 Robotic Liquid Handler. Our method utilizes a simple sample preparation technique, utilizing only 20 μL of a serum sample, to accurately measure Bupropion, Citalopram, Desipramine, Imipramine, Olanzapine, Sertraline and Vilazodone across a range of 1.0 to 230 ng/mL. Our method exhibits a linearity of R2 ≥ 0.99 when detected in MRM mode and % CV of ≤ 20% for all analytes across the board. In addition, we have designed a prototype that can be utilized at a clinical mass spectrometry lab and assessed the long-term use of this prototype using an accelerated stability study. Overall, our developed method has the potential to be translated to clinical settings to monitor postpartum depression for a large number of patient samples using automation.

摘要

抑郁症是一个日益严重的全球性危机,女性的诊断率高于男性。尽管过去二十年来,开处抗抑郁药的患者比例增加了两倍,但我们仍处于一个十字路口,即找到适合患者的药物与监测药物在体内的丰度以防止不良反应之间存在差距。液相色谱串联质谱法(LC-MS/MS)已引起临床医生的关注,因为它是一种具有高特异性和准确性的技术,可以准确监测人血清中的治疗性药物。这可能是一个潜在的解决方案,但挑战仍然存在于样品制备领域,需要找到一种可自动化的方法。我们已经开发并验证了一种基于 LC-MS/MS 的测定方法,用于同时定量女性中 4 种常用抗抑郁药,该方法使用 JANUS G3 机器人液体处理机实现自动化。我们的方法使用简单的样品制备技术,仅使用 20 μL 血清样本,即可准确测量 Bupropion、Citalopram、Desipramine、Imipramine、Olanzapine、Sertraline 和 Vilazodone 的浓度范围为 1.0 至 230 ng/mL。该方法在 MRM 模式下检测时具有线性度 R2≥0.99,所有分析物的 CV%≤20%。此外,我们设计了一个原型,可以在临床质谱实验室中使用,并通过加速稳定性研究评估该原型的长期使用情况。总体而言,我们开发的方法有可能通过自动化应用于临床环境,以监测大量患者样本的产后抑郁症。

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