建立同时定量小鼠血浆中11种全氟烷基化合物的LC-MS/MS方法，用于毒性动力学应用。

IF 3.1 3区医学 Q2 CHEMISTRY, ANALYTICAL

Journal of pharmaceutical and biomedical analysis Pub Date : 2024-11-30 DOI:10.1016/j.jpba.2024.116596

Chloé ML. Argoul , Yannick Dauwe , Laïla Lakhal , Pierre-Louis Toutain , Nicole Picard-Hagen , Véronique Gayrard , Marlène Z. Lacroix

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引用次数: 0

摘要

在监管压力下，长链全氟烷基和多氟烷基物质（PFAS）的生产已被逐步淘汰，短链同系物和醚-PFAS等替代品已取代了生物蓄积性长链PFAS。然而，缺乏关于某些PFAS的毒性动力学（TK）特性的数据，特别是长链化合物的新兴替代品。此外，用于传统知识研究的现有分析方法只能同时测量一种或几种化合物。因此，我们开发了一种LC-MS/MS方法，用于同时定量小鼠血浆中11种PFAS，这些PFAS代表了这些化合物中一些最重要的类别，用于TK研究。根据欧洲药品管理局的指南，该方法在0.5-1000 ng/mL范围内成功验证，并应用于在小鼠中进行的24小时试点TK研究。在试点研究中，所有化合物在24 小时内被监测。因此，本方法适用于血浆样品中PFAS的同时定量，可用于未来的TK研究。

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Development of an LC-MS/MS method for the simultaneous quantification of 11 perfluoroalkyl compounds in mouse plasma for toxicokinetic applications

Following regulatory pressure, the manufacture of long-chain per- and polyfluoroalkyl substances (PFAS) has been phased out, and alternatives such as short-chain homologs and ether-PFAS have replaced the bioaccumulative long-chain PFAS. However, data are lacking regarding the toxicokinetic (TK) properties of certain PFAS, particularly emergent substitutes for long-chain compounds. Additionally, the existing analytical methods used for TK studies measure a single compound or only a few simultaneously. For this reason, an LC-MS/MS method was developed for the simultaneous quantification in mouse plasma of 11 PFAS representative of some of the most important categories of these compounds, for application in TK studies. The method was successfully validated in the range of 0.5–1000 ng/mL, in accordance with the European Medicines Agency guidelines, and applied to a 24-h pilot TK study conducted in mice. All compounds were monitored over 24 hours in the pilot study. The present method is therefore suitable for the simultaneous quantification of PFAS in plasma samples and can be applied for future TK studies.

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来源期刊

Journal of pharmaceutical and biomedical analysis 医学-分析化学

CiteScore

6.70

自引率

5.90%

发文量

588

审稿时长

37 days

期刊介绍： This journal is an international medium directed towards the needs of academic, clinical, government and industrial analysis by publishing original research reports and critical reviews on pharmaceutical and biomedical analysis. It covers the interdisciplinary aspects of analysis in the pharmaceutical, biomedical and clinical sciences, including developments in analytical methodology, instrumentation, computation and interpretation. Submissions on novel applications focusing on drug purity and stability studies, pharmacokinetics, therapeutic monitoring, metabolic profiling; drug-related aspects of analytical biochemistry and forensic toxicology; quality assurance in the pharmaceutical industry are also welcome. Studies from areas of well established and poorly selective methods, such as UV-VIS spectrophotometry (including derivative and multi-wavelength measurements), basic electroanalytical (potentiometric, polarographic and voltammetric) methods, fluorimetry, flow-injection analysis, etc. are accepted for publication in exceptional cases only, if a unique and substantial advantage over presently known systems is demonstrated. The same applies to the assay of simple drug formulations by any kind of methods and the determination of drugs in biological samples based merely on spiked samples. Drug purity/stability studies should contain information on the structure elucidation of the impurities/degradants.