他唑巴坦钠原料药中未知杂质的质谱结构研究

Structure Study of Unknown Impurities by Mass Spectrometry in Tazobactam Sodium Bulk Drug

利用质谱引导的纯化仪富集、纯化他唑巴坦钠原料药中含量超过0.1%的未知杂质,通过电喷雾高分辨质谱获得的特征离子信息,对其进行结构推测,检测到的2个新杂质化学结构可能为3-甲基-7-氧代-3-叠氮甲基-4-硫杂-1-氮杂双环[3.2.0]庚烷-2-羧酸4,4-二氧化物(杂质Ⅰ)和3-甲基-7-氧代-3-氯甲基-4-硫杂-1-氮杂双环[3.2.0]庚烷-2-羧酸4,4-二氧化物(杂质Ⅱ)。同时建立了一种液相色谱方法,该方法优于现行标准,能实现他唑巴坦钠与其有关物质的更好分离,为他唑巴坦钠原料药的质量标准提升和工艺参数优化提供了依据。

A mass spectrometer guided purification apparatus was used to enrich and purify the unknown impurities, whose content was over 0.1% in tazobactam sodium bulk drug. The specified abundant information of fragment ions was obtained by electrospray high resolution mass spectrometry for the structure elucidation of the unknown impurities. The structures of two impurities were referred as 3-methyl-7-oxo-3-azidomethyl-4-thia-1-azabicyclo[3.2.0]-heptane-2-carboxylic acid 4,4-dioxide(impurityⅠ) and 3-methyl-7-oxo-3-chloromethyl-4-thia-1-azabicyclo[3.2.0]-heptane-2-carboxylic acid 4,4-dioxide(impurityⅡ). The standard was also optimized by a new HPLC method, to achieve better resolution of tazobactam sodium and its related substances, which could provide a basis for the quality standard improvement and process parameters optimization of tazobactam sodium bulk drug.