Isolation and structural characterization of eight impurities in aztreonam

IF 3.1 3区医学 Q2 CHEMISTRY, ANALYTICAL

Journal of pharmaceutical and biomedical analysis Pub Date : 2022-02-20 DOI:10.1016/j.jpba.2022.114587

Yahui Li , Minghua Yuan , Dong Ding , Xiong Jiang , Qing Ye , Fujiang Guo

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引用次数: 1

Abstract

To comply with regulatory requirements, it is necessary to detect and separate the impurities generated during aztreonam synthesis or storage. The chromatogram of aztreonam revealed eight major impurities, which were purified through medium-pressure reversed-phase column and preparative High Performance Liquid Chromatography (HPLC). Through high resolution electrospray ionization mass spectroscopy (HRESIMS), as well as one- and two-dimensional nuclear magnetic resonance (NMR), their structures were confirmed as aztreonam acetate (Ⅰ), desulfated aztreonam (Ⅱ), anti-aztreonam (Ⅲ), open-ring aztreonam (Ⅳ), open-ring desulfated aztreonam (Ⅴ), open-ring desulfated aztreonam ethyl ester (VI), cis-deamino open-ring desulfated aztreonam (VII), and trans-deamino open-ring desulfated aztreonam (Ⅷ). Their exact concentrations were determined through quantitative nuclear magnetic resonance (qNMR) technique. Structural elucidation of the eight impurities through ¹H NMR, ¹³C NMR, the ¹H-¹H COSY, NOESY, HSQC, HMBC NMR and MS spectra was conducted. Especially, ⅥI and Ⅷ were identified as undescribed impurities here.

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氮曲南中8种杂质的分离与结构表征

为了符合法规要求，有必要对氨曲南合成或储存过程中产生的杂质进行检测和分离。通过中压反相柱和制备型高效液相色谱(HPLC)对氮曲南的8种主要杂质进行了纯化。通过高分辨率电喷雾电离质谱(hresms)以及一、二维核磁共振(NMR)，确定了它们的结构为:醋酸氮曲南(Ⅰ)、脱硫氮曲南(Ⅱ)、抗氮曲南(Ⅲ)、开环氮曲南(Ⅳ)、开环脱硫氮曲南(Ⅴ)、开环脱硫氮曲南乙酯(VI)、顺式脱氨基开环脱硫氮曲南(VII)、和反式脱氨基开环脱硫氨曲南(Ⅷ)。通过定量核磁共振(qNMR)技术测定了它们的确切浓度。通过1H NMR、13C NMR、1H-1H COSY、NOESY、HSQC、HMBC NMR和MS谱对8种杂质进行了结构解析。特别是，ⅥI和Ⅷ在这里被确定为未描述的杂质。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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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.