非索非那定光降解产物的分离与结构解析

Isolation and structure elucidation of photodegradation products of fexofenadine.

作者信息

Breier Ana Rita, Nudelman Norma Sbarbati, Steppe Martin, Schapoval Elfrides Eva Scherman

机构信息

Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Av. Ipiranga, 2752 Lab. 402, Porto Alegre-RS, CEP 90610-000, Brazil.

出版信息

J Pharm Biomed Anal. 2008 Jan 22;46(2):250-7. doi: 10.1016/j.jpba.2007.09.017. Epub 2007 Sep 25.

DOI:10.1016/j.jpba.2007.09.017

PMID:17977686

Abstract

The photostability of the antihistamine fexofenadine hydrochloride is described. The stress studies revealed the photostability of the drug as the most adverse stability factor. The main photodegradation products were isolated and its structures were elucidated by 1H, 13C, COSY, HSQC, HMBC NMR and mass spectrometry techniques. The drug was exposed to UVC light at 254 nm in methanolic solutions and the degradation was followed by HPLC and TLC. The photostability of fexofenadine tablets was studied and the same degradation products were observed. The two photodegradation products isolated were characterized as the isopropyl derivative, obtained by decarboxilation of fexofenadine, and a benzophenone compound, which was obtained by rearrangement of aromatic rings and oxidation reactions. The results show the importance of appropriate light protection during the drug development process, storage and handling.

摘要

描述了抗组胺药盐酸非索非那定的光稳定性。加速试验表明，该药物的光稳定性是最不利的稳定性因素。分离出主要的光降解产物，并通过1H、13C、COSY、HSQC、HMBC核磁共振和质谱技术阐明其结构。将该药物在甲醇溶液中于254nm的紫外线灯下照射，通过高效液相色谱法（HPLC）和薄层色谱法（TLC）跟踪降解情况。研究了非索非那定片的光稳定性，并观察到相同的降解产物。分离出的两种光降解产物分别被鉴定为非索非那定脱羧得到的异丙基衍生物，以及通过芳环重排和氧化反应得到的二苯甲酮化合物。结果表明在药物研发、储存和处理过程中进行适当的光保护非常重要。