Separation and Characterization of Novel Degradation and Process Related Impurities of Bedaquiline Bulk Drug

Abstract

Bedaquiline (BDQ) is a new drug approved by United States Food and Drug Administration (USFDA) in 2012 for the treatment of drug-resistant tuberculosis, which has become a major threat globally. The manuscript presents the development of three liquid chromatography (LC) based analytical methods. The first is a stability indicating RP-HPLC (reverse phase-high performance liquid chromatography) method to analyze the BDQ in presence of its degradation products. Another UPLC/ESI–MS (ultra-performance liquid chromatography/electron spray ionization–mass spectrometry) method was developed for the identification of different degradation based and process related impurities and the third, preparative HPLC method was developed for the isolation of major degradation products. Eleven degradation products and one process related impurity were identified using UPLC/ESI–MS whereas preparative HPLC was used to isolate two degradation products and their chemical structure was elucidated using nuclear magnetic resonance, mass and infra-red spectral data.

Quantitative Study of Impurities in Bedaquiline Fumarate: Identification and Characterization of Its Three Degradation Products Using HPLC, LC/ESI-MS, and NMR Analyses

“…1 . 8 However, analysis methods of BDQ have not been included in the pharmacopeias of any countries, and reported only in a few literatures, such as separation and characterization of its degradation impurities, 9 10 analysis of its related substances by high-performance liquid chromatography (HPLC), 11 separation of its diastereomers by reversed-phase-HPLC, 12 and determination of BDQ in human serum by liquid chromatography-tandem mass spectrometry (LC-MS/MS). 13 Therefore, studies of BDQ quality control, especially the study of BDQ-related substances, could help meet the production goals, and are also important and necessary for further development of the drug.…”