Quality by Design Based Chromatography Technique Development and Validation for the Medicine Venetoclax (for Chronic Leukemia), in the Context of Impurities Including Degradation Products.

Journal: Biomedical Chromatography : BMC
Published:
Abstract

The present research study describes the Venetoclax (VEN)-related substances test method using RP-HPLC/DAD techniques. It was developed and validated according to ICH Q14 and Q2(R2) guidelines. The substances were separated using an X-Bridge Phenyl column (150 mm × 4.6 mm, 3.5 μm) and a gradient program. The mobile phase A, consist 0.02 mM Na2HPO4 (pH 8.0) buffer and acetonitrile in an 80:20 v/v ratio. Mobile phase B was prepared using a 75:25 v/v mixture of acetonitrile and a pH 8.0 buffer and well mixed. The flow rate remains constant at 1.0 mL/min, traversing an appropriate gradient program. The VEN and its impurities were detected at 280 nm, with an injection volume of 15 μL and a runtime of 130 min. Moreover, we identified proper degradation impurities and sensitivity of VEN due to forced-degradation study experiments. The linearity and range of the testing procedure were validated by computing r2 values over 0.999. All organic impurities were recovered at a rate of 97.6%-106.0% with a relative standard deviation of 0.11%-4.35%. A robustness test was conducted utilizing the AQbD methodology. The proposed method was stability-indicating in nature and can be used for commercial samples in the pharmaceutical industries.

Authors
Rajeshwari Dandabattina, Karuna Merugu, Lova Gani Bandaru, Haridasyam Sharathbabu, Rambabu Gundla, Naresh Katari
Relevant Conditions

Leukemia