Rapid structure elucidation of drug degradation products using mechanism-based stress studies in conjunction with LC–MSⁿ

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• 作者：Mingxiang Lin ; Min Li ; Alexei V. Buevich ; Rebecca Osterman ; Abu M. Rustum
• 关键词：Betamethasone dipropionate ; Lumibetamethasone dipropionate ; Photodegradation ; LC– ; MS ; NMR ; Stress study
• 刊名：Journal of Pharmaceutical and Biomedical Analysis
• 出版年：2009
• 出版时间：15 October 2009
• 年：2009
• 卷：50
• 期：3
• 页码：275-280
• 全文大小：629 K

文摘

Betamethasone dipropionate is an active pharmaceutical ingredient (API) that is used in various dosage forms of finished products for the treatment of inflammatory disorders. An unknown degradant was observed during a solution stability study of betamethasone dipropionate. An approach that combines LC–MSⁿ, mechanism-based stress studies, semi-preparative HPLC purification and structure elucidation by NMR spectroscopy was used to identify the unknown species. The key step of this approach is the design of relevant stress studies based on the plausible degradation mechanism that is revealed by the informative LC–MSⁿ analysis. The appropriately designed mechanism-based stress studies not only verify the degradation mechanism but also produce enough quantities of the unknown species for further structure elucidation/confirmation by NMR spectroscopy. With this strategy, the unknown degradant was rapidly identified as lumibetametasone dipropionate, a photodegradation product of betamethasone dipropionate.