Comprehensive degradation profiling and influence of different oxidizing reagents on tinoridine hydrochloride: Structural characterization of its degradation products using HPLC and HRMS

Abstract

Rationale Stress testing on tinoridine hydrochloride was carried out using a multidimensional approach. This included different conditions: hydrolytic (acidic, alkaline, and neutral conditions), different oxidative reagents, thermal, photolytic conditions, HPLC method development, and structural elucidation using high‐resolution mass spectrometry (HRMS). It provides the basis for quality control of tinoridine hydrochloride and its derivatives during storage conditions. Methods The tinoridine hydrochloride was subjected to a variety of stress conditions. A gradient reversed‐phase HPLC method was developed on a X‐Bridge C18 column (250 × 4.6 mm, 5 μm) to separate all the degradation products (DPs). HRMS studies have been performed to elucidate the structure of DPs. Results HPLC‐PDA study revealed that significant degradation products were formed in hydrolytic, AIBN (radical initiator at 40°C), thermal, and solid‐state photolight stress conditions, but the drug was stable under oxidative conditions (H2O2, Fenton's reagent at room temperature and ferric chloride at 40°C). The structure of degradation products was elucidated, and mechanism of their formation was explained. Conclusion Stress study was successfully carried out as per ICH Q1A (R2) guideline on tinoridine hydrochloride. A total of six new degradation products were characterized, DP 2 and DP 6 formed by the effect of co‐solvent. This study provides the scientifically sound basis for quality monitoring and storage conditions of tinoridine hydrochloride.

Characterization of potential degradation products of brexpiprazole by liquid chromatography/quadrupole–time‐of‐flight mass spectrometry and nuclear magnetic resonance, and prediction of their physicochemical properties by ADMET Predictor™

“…For the three isolated DPs, support was obtained additionally using nuclear magnetic resonance (NMR). [10][11][12][13] Once the structures of all the DPs were established, an effort was made to postulate the drug degradation pathways and the degradation mechanisms. Finally, physicochemical properties and toxicity of BRZ and its DPs were envisioned in silico by using ADMET Predictor™ software.…”

“…The 12 DPs formed were separated on a chromatography column and were characterized with the help of data generated using liquid chromatography /quadrupole–time‐of‐flight mass spectrometry (LC/Q‐TOF‐MS). For the three isolated DPs, support was obtained additionally using nuclear magnetic resonance (NMR) 10–13 . Once the structures of all the DPs were established, an effort was made to postulate the drug degradation pathways and the degradation mechanisms.…”