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

基于质量源于设计的色谱技术开发与验证,用于检测药物维奈托克(用于治疗慢性白血病)中的杂质,包括降解产物

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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 r(2) 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.

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