INVESTIGATION OF FORCED DEGRADATION PRODUCTS OF ETODOLAC BY LC AND LC-MS/MS

摘要

Objective: The main objective of this study was to investigate the degradation products (DPs) of Etodolac (ETD) API under different stress conditions (acid hydrolysis, base hydrolysis, oxidation, thermal and photolysis) and to characterize the major DPs using Liquid Chromatography-tandem Mass Spectrometry (LC-MS/MS) and Infrared (IR) spectroscopy. Methods: The proposed study describes a reversed-phase LC and LC-MS/MS method. Separation of ETD and its DPs was achieved on a Phenomenex C18 column. Structures of the major DPs were studied using a Triple Quadrupole Mass Spectrometer. A separate gradient LC-MS/MS method was developed for this purpose. The analysis was done using Shim-pack XR ODS column. Possible chemical reactions were predicted depending on the degradation type and the fragmentation data obtained from LC-MS/MS. Major DPs were isolated using preparative LC technique. These DPs were obtained in solid form using rotavap and lyophilizer and were then analyzed by IR spectroscopy to confirm their structural details. Results: ETD was found to degrade completely under acid hydrolysis; it degraded 68 % under oxidation, 25 % after photolysis, 6 % in basic conditions and less than 1 % in thermal degradation. Four major DPs were characterized using LC-MS/MS and IR spectroscopy. Conclusion: The DPs of ETD were investigated and characterized. Also, the tentative degradation pathways of ETD under different stress conditions were postulated. Keywords: Etodolac, Forced degradation studies, Degradation products, LC, LC-MS/MS