6-氨基青霉素酸相关物质的UPLC-Q-Exactive Orbitrap-MS/MS和NMR表征。

IF 3.1 3区医学 Q2 CHEMISTRY, ANALYTICAL

Journal of pharmaceutical and biomedical analysis Pub Date : 2025-09-11 DOI:10.1016/j.jpba.2025.117143

Jiajie Wu , Jing Lu , Ju Liu , Huimin Yi , Ben Zhou , Hua Chang , Hongjuan Pan

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引用次数: 0

摘要

6-氨基青霉素酸（6-APA）是合成半合成青霉素抗生素的关键中间体，在热、碱性、酸性、氧化和光解条件下被强制降解。通过超高压液相色谱-四极杆萃取轨道阱质谱（UPLC-Q-Exactive Orbitrap-MS/MS）和核磁共振（NMR）技术对降解产物进行鉴定。采用半制备液相色谱（semi- prepare - lc）分离纯化了一种氧化强制降解的6-APA，命名为RS7。结构表征证实RS7为二硫化青霉胺。共鉴定出18种相关物质，其中工艺相关物质3种（含2对异构体），降解产物14种（含5对异构体）。提出并总结了6-APA的降解途径。首次鉴定了6-APA的氧化和还原降解产物，包括在其强制降解产物中新检测到二硫化青霉胺。

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Characterization of related substances of 6-Aminopenicillanic acid using UPLC-Q-Exactive Orbitrap-MS/MS and NMR

6-Aminopenicillanic acid (6-APA), a key intermediate in the synthesis of semi-synthetic penicillin antibiotics, was subjected to forced degradation under thermal, alkaline, acidic, oxidative, and photolytic conditions. The resulting degradation products were identified by ultra high-pressure liquid chromatography-quadrupole-Exactive Orbitrap mass/mass spectrometry (UPLC-Q-Exactive Orbitrap-MS/MS) and nuclear magnetic resonance (NMR) techniques. An oxidative forced degradation of 6-APA, designated RS7, was isolated and purified using semi-preparative liquid chromatography (semi-Prep-LC). Structural characterization confirmed RS7 as penicillamine disulfide. A total of 18 related substances were identified, comprising three process-related substances (including 2 pairs of isomers), and 14 degradation products (including 5 pairs of isomers). The degradation pathways of 6-APA were proposed and summarized. For the first time, the oxidative and reductive degradation products of 6-APA were identified, including the new detection of penicillamine disulfide among its forced degradation products.

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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.