使用 UPLC-MS/MS 对人血浆中的丁丙诺啡、诺丁诺啡及其共轭代谢物进行简化处理和快速定量:评估阿片类药物使用障碍治疗期间的丁丙诺啡暴露情况。

IF 1.9 3区 化学 Q3 BIOCHEMICAL RESEARCH METHODS
Wenchen Zhao, Osama Y. Alshogran, Hongfei Zhang, Anand Joshi, Elizabeth E. Krans, Steve Caritis, Imam H. Shaik, Raman Venkataramanan
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引用次数: 0

摘要

阿片类药物使用障碍(OUD)是一种慢性神经行为疾病,在妊娠期很常见。阿片类药物使用障碍通常采用美沙酮或丁丙诺啡(BUP)治疗。众所周知,妊娠会改变药物的药代动力学,并可能导致药物暴露和反应的改变。一种简单、特异、灵敏的分析方法可用于测量母体药物及其代谢物,这对于评估妊娠对药物暴露的影响非常重要。针对人血浆中的 BUP 及其主要代谢物(诺丁诺啡 [NBUP]、丁丙诺啡-葡萄糖醛酸苷 [BUP-G] 和诺丁诺啡-葡萄糖醛酸苷 [NBUP-G]),我们开发并验证了一种新的液相色谱-串联质谱分析方法,该方法利用简单的蛋白质沉淀程序进行样品制备,并采用四种氚代内标进行定量。在 0.05-100 ng/mL 的浓度范围内,BUP 和 NBUP 的标准曲线呈线性;在 0.1-200 ng/mL 的浓度范围内,BUP-G 和 NBUP-G 的标准曲线呈线性。所有分析物的日内和日间偏差和精密度均在标称值的±15%以内。四级质量控制评估显示,所有分析物的回收率都很高,基质效应极小。在测试的各种实验室条件下,都观察到了分析物的充分稳定性。总之,所开发的方法简便、灵敏、准确、重现性好,成功地应用于一项评估OUD治疗期间BUP暴露的临床研究中孕妇血浆样本中BUP及其代谢物的定量分析。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Simplified processing and rapid quantification of buprenorphine, norbuprenorphine, and their conjugated metabolites in human plasma using UPLC–MS/MS: Assessment of buprenorphine exposure during opioid use disorder treatment

Opioid use disorder (OUD) is a chronic neurobehavioral ailment and is prevalent in pregnancy. OUD is commonly treated with methadone or buprenorphine (BUP). Pregnancy is known to alter the pharmacokinetics of drugs and may lead to changes in drug exposure and response. A simple, specific, and sensitive analytical method for measuring the parent drug and its metabolites is valuable for assessing the impact of pregnancy on drug exposure. A new liquid chromatography–tandem mass spectrometric method that utilized a simple protein precipitation procedure for sample preparation and four deuterated internal standards for quantification was developed and validated for BUP and its major metabolites (norbuprenorphine [NBUP], buprenorphine-glucuronide [BUP-G], and norbuprenorphine-glucuronide [NBUP-G]) in human plasma. The standard curve was linear over the concentration range of 0.05–100 ng/mL for BUP and NBUP, and 0.1–200 ng/mL for BUP-G and NBUP-G. Intra- and inter-day bias and precision were within ±15% of nominal values for all the analytes. Quality controls assessed at four levels showed high recovery consistently for all the analytes with minimal matrix effect. Adequate analyte stability was observed at various laboratory conditions tested. Overall, the developed method is simple, sensitive, accurate and reproducible, and was successfully applied for the quantification of BUP and its metabolites in plasma samples collected from pregnant women in a clinical study assessing BUP exposure during OUD treatment.

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来源期刊
Journal of Mass Spectrometry
Journal of Mass Spectrometry 化学-光谱学
CiteScore
5.10
自引率
0.00%
发文量
84
审稿时长
1.5 months
期刊介绍: The Journal of Mass Spectrometry publishes papers on a broad range of topics of interest to scientists working in both fundamental and applied areas involving the study of gaseous ions. The aim of JMS is to serve the scientific community with information provided and arranged to help senior investigators to better stay abreast of new discoveries and studies in their own field, to make them aware of events and developments in associated fields, and to provide students and newcomers the basic tools with which to learn fundamental and applied aspects of mass spectrometry.
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