Quantification of MDR-TB drug JBD0131 and its metabolite in plasma via UPLC-MS/MS: application in first-in-human study.

IF 1.9 4区医学 Q3 BIOCHEMICAL RESEARCH METHODS Bioanalysis Pub Date : 2024-12-01 Epub Date: 2024-10-07 DOI:10.1080/17576180.2024.2404311

Tiantao Gao, Xiaoxue Ou, Jia Miao, Yongping Qin

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Abstract

Aim: JBD0131, a novel anti-multidrug-resistant tuberculosis (MDR-TB) drug, can target and inhibit the synthesis of mycolic acids, which are crucial components of the cell wall of the Mycobacterium tuberculosis complex. To support the results of this clinical trial in healthy subjects, development of a specific and accurate quantification method for detecting JBD0131 and its metabolite DM131 in human plasma is needed.Materials & methods: Samples with prior added stabilizer were pretreated by protein precipitation method and the extracts were subjected to ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The m/z transitions for the precursor/product ion pairs were 402.1/273 for JBD0131, 333.1/273 for DM131 and 386.1/257 for the internal standard (IS).Results: This method showed good linearity from 1 to 2000 ng/ml for JBD0131 and 0.25 to 500 ng/ml for DM131 and was validated in terms of selectivity, linearity, accuracy, precision, matrix effect, recovery of pretreament and stability.Conclusion: This method was sensitive and specific for measuring the plasma concentrations of JBD0131 and its metabolites. And it was applied for the investigation of the pharmacokinetics of JBD0131 and DM131 in a clinical trial.

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通过 UPLC-MS/MS 对血浆中的 MDR-TB 药物 JBD0131 及其代谢物进行定量：在首次人体试验中的应用。

目的：JBD0131是一种新型抗耐多药结核病（MDR-TB）药物，它能靶向抑制霉酚酸的合成，而霉酚酸是结核分枝杆菌复合体细胞壁的重要组成部分。为了支持这项在健康受试者中进行的临床试验的结果，需要开发一种特异、准确的定量方法来检测人体血浆中的 JBD0131 及其代谢物 DM131：采用蛋白质沉淀法对预先添加了稳定剂的样品进行预处理，然后将提取物进行超高效液相色谱-串联质谱（UPLC-MS/MS）分析。JBD0131 的前体/产物离子对的 m/z 过渡为 402.1/273，DM131 为 333.1/273，内标（IS）为 386.1/257：该方法在 JBD0131 和 DM131 的选择性、线性、准确度、精密度、基质效应、前处理剂回收率和稳定性等方面进行了验证：该方法对JBD0131及其代谢物的血浆浓度测定灵敏、特异。结论：该方法对JBD0131及其代谢物的血浆浓度测定灵敏、特异，可用于临床试验中JBD0131和DM131的药代动力学研究。

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来源期刊

Bioanalysis BIOCHEMICAL RESEARCH METHODS-CHEMISTRY, ANALYTICAL

CiteScore

3.30

自引率

16.70%

发文量

审稿时长

2 months

期刊介绍： Reliable data obtained from selective, sensitive and reproducible analysis of xenobiotics and biotics in biological samples is a fundamental and crucial part of every successful drug development program. The same principles can also apply to many other areas of research such as forensic science, toxicology and sports doping testing. The bioanalytical field incorporates sophisticated techniques linking sample preparation and advanced separations with MS and NMR detection systems, automation and robotics. Standards set by regulatory bodies regarding method development and validation increasingly define the boundaries between speed and quality. Bioanalysis is a progressive discipline for which the future holds many exciting opportunities to further reduce sample volumes, analysis cost and environmental impact, as well as to improve sensitivity, specificity, accuracy, efficiency, assay throughput, data quality, data handling and processing. The journal Bioanalysis focuses on the techniques and methods used for the detection or quantitative study of analytes in human or animal biological samples. Bioanalysis encourages the submission of articles describing forward-looking applications, including biosensors, microfluidics, miniaturized analytical devices, and new hyphenated and multi-dimensional techniques. Bioanalysis delivers essential information in concise, at-a-glance article formats. Key advances in the field are reported and analyzed by international experts, providing an authoritative but accessible forum for the modern bioanalyst.