College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang, 310058, China.
Zhejiang Guobang Pharmaceutical Co. Ltd., Shangyu, Zhejiang, 312300, China.
J Pharm Biomed Anal. 2021 Feb 20;195:113853. doi: 10.1016/j.jpba.2020.113853. Epub 2020 Dec 17.
Azithromycin is a macrolide antibiotic which is used to treat a wide variety of bacterial infections. Impurity P is one of the impurities in azithromycin product, which is registered in Pharmacopoeias of Europe and USA. However, to date, the structure of this impurity has still not been elucidated. In this work, we separated impurity P from azithromycin product using preparative chromatography and successfully identified its chemical structure using multiple analytical techniques. First, high-resolution ion trap-time-of-flight mass spectrometry (IT-TOF MS) was used to determine the accurate molecular mass ([M+H]m/z 777.5121) and the chemical formula (CHNO) of the impurity. Second, Fourier transforming infrared spectroscopy (FT-IR), ultraviolet-visible absorption spectroscopy (UV-vis) and tandem mass spectrometry (MS/MS) analyses were performed to probe into the key functional groups of the impurity to aid the NMR analysis. Finally, the structure of the impurity was successfully resolved using multidimensional NMR. In addition, a mechanism for the formation of this impurity was proposed.
阿奇霉素是一种大环内酯类抗生素，用于治疗多种细菌感染。杂质 P 是阿奇霉素产品中的一种杂质，已在欧洲和美国药典中注册。然而，迄今为止，该杂质的结构仍未阐明。在这项工作中，我们使用制备色谱法从阿奇霉素产品中分离出杂质 P，并使用多种分析技术成功鉴定了其化学结构。首先，高分辨率离子阱飞行时间质谱（IT-TOF MS）用于确定杂质的准确分子量（[M+H]+ m/z 777.5121）和化学式（CHNO）。其次，进行傅里叶变换红外光谱（FT-IR）、紫外可见吸收光谱（UV-vis）和串联质谱（MS/MS）分析，以探究杂质的关键官能团，辅助 NMR 分析。最后，使用多维 NMR 成功解析了杂质的结构。此外，还提出了该杂质的形成机制。
