Oxidative degradation profile studies of Tavaborole by a validated stability indicating RP-UPLC method: Isolation and characterization of novel degradant using 2D-NMR and HRMS.

Abstract

The current research work reports the study on the degradation profile of Tavaborole, which is an oxaborole antifungal drug used to treat infections in the toenails. This work also reports the chemical stability of Tavaborole in different stress conditions along with isolation and characterization of degradation products by high resolution mass spectrometry (HRMS) and 2D NMR techniques. A sensitive and reproducible stability indicating Ultra Performance Liquid Chromatography (UPLC) method is developed and validated for quantification of Tavaborole bulk drug in the presence of degradation products. Significant degradation was observed during oxidative stress conditions using H2 O2 . It is observed that the drug is highly unstable under oxidation stress conditions and thus degradation profiles with various oxidizing reagents were studied. One unknown impurity (DP-1) was formed during peroxide degradation which was isolated by reverse phase preparative chromatography. The structure of this degradant was characterized by high resolution mass spectrometry and multidimensional NMR techniques. The structure of this novel impurity DP-1 was identified as (4-fluoro-2-(hydroxymethyl) phenol) which was not reported as a degradant in literature. An Acquity BEH C18; 100 x 2.1mm; 1.7 μm column was used to achieve desired separation within a shorter runtime of 4.0 minutes. The method was validated for specificity, precision, linearity, and accuracy over the concentration range of 5.0-400 μg mL-1 (r2 -0.9999) and LOQ 5.0 μg mL-1 . This method is compatible with LCMS analysis which enables to identify the unknown impurities formed in the process.