Characterization of degradation products of Macozinone by LC–MS/MS and elucidation of their degradation pathway

Abstract

Macozinone has high activity against tuberculosis and is a promising candidate compound with a new target DprE1for the treatment of tuberculosis. This study described the degradation behavior of Macozinone. Macozinone was subjected to forced degradation in solid-state and solution-state under oxidative, thermal, hydrolytic (alkaline and acidic) and photolytic conditions. A total of nineteen DPs were detected. When Macozinone in solid-state and solution-state was treated with oxidative degradation condition, seven DPs were detected. Three DPs were found from Macozinone in the solution-state under thermal degradation condition, and five DPs were discovered in the solution-state under alkaline degradation condition. Both the solid-state and solution-state degradation of Macozinone detected two DPs under acidic degradation condition. Macozinone was highly unstable under photolytic degradation condition, as nine DPs in all were found when exposed to strong light in solid-state and solution-state. No obvious DPs were observed under alkaline and thermal degradation conditions from Macozinone in solid-state. All DPs were characterized based on LC-MSn and LC-HRMS/MS techniques. The degradation mechanism and pathway of Macozinone were discussed and summarized. To the best of our knowledge, the DPs of Macozinone were identified for the first time.