Development and Validation of an Environmentally Benign and Robust Stability Indicating Assay Method for Lenalidomide: Comprehensive Degradation Kinetics Study and Application of Synergistic Approach Involving Green Analytical Chemistry and Quality by Design Methodology
Indian Journal of Pharmaceutical Education and Research
Abstract
Objective: A state of the art, robust and environmentally benign stability indicating assay method (SIAM) has been developed for model drug Lenalidomide (LEN). Methods: A Green metrics assessment was conducted by environment assessment tool (EAT), analytical method volume intensity (AMVI) and Ecosolvent® tool. Successful chromatographic separation was accomplished on a Thermo C18 GAC column having dimensions of 4.6×150 mm and 3μ particle size using green solvents viz., methanol and acetate buffer in the ratio of 85:15. Results: The obtained EAT score and AMVI were 32.19 and 24 mL respectively. A green SIAM was developed and it was validated as per ICH Q2 (R1) guidelines. Quality by Design (QbD) approach was incorporated at validation stage to prove the robustness of the developed green method by applying 2^5-2 Res III 2- level fractional factorial design (FFD). Conclusion: An extensive stress degradation study along with degradation kinetics were performed and probable degradation pathways were predicted.
Keywords
- Lenalidomide
- Green analytical chemistry
- Quality by Design
- Degradation
- kinetics
- LC-MS/MS