Development and Validation of a Stability-indicating Method for Ibrutinib: Identification and Separation of Degradation Products, Known and Genotoxic Impurities Using RP-HPLC/PDA and QDa Mass Detectors

Abstract

The present work describes a novel stability-indicating method development and validation for separation and identification of degradation products, known and genotoxic impurities in recently FDA approved (Ibrutinib) an anti-cancer drug using RP-HPLC/PDA and QDa mass detectors. Separation of all impurities could be achieved using stationary phase column (X-Select CSH, C18, 150 mm × 4.6 mm × 3.5 μm) with a flow rate of 1 ml/minute and total run time 85 minutes. Degradation was carried out; Ibrutinib was sensitive to acid, base and peroxide conditions. In the base degradation sample, a major degradation impurity was found, which was identified their mass value and structure information using QDa mass detector. Ibrutinib was found to be stable under heat, UV, humidity and water conditions. No interference was found at identified impurities, degradation products and ibrutinib peak retention time. The proposed method was validated as per ICH Q2 (R1) guidelines. It was observed that the percentage recovery was found to be 95 % to 105 % and linearity over the range of LOQ level, 50 %, 100 % 150 % and 300 % level of concentrations with R²: 0.999 to 1.000. According to validation and degradation results, the method was found to be good stability indicating nature as well as user-friendly.

Key words:

• Ibrutinib degradation products
• finished dosage form
• X-select CSH column
• force degradation study
• liquid chromatography