Quality by Design based Development and Validation of RP-HPLC Method for Simultaneous Estimation of Sitagliptin and Metformin in Bulk and Pharmaceutical Dosage Forms

摘要

Objectives: This paper portrays a recently developed, optimized and validated isocratic RP-HPLC strategy for the separation of two antidiabetic drugs (sitagliptin and metformin) in bulk and pharmaceutical formulations with the aid of quality by design and multi-criteria decision making approach. Methods: The effective chromatographic separation was accomplished by utilizing the Monolithic C 18 segment (100×4.6 mm id, 5μm molecule size) and PDA-UV- detection at 210nm.The scope of independent variables utilized for the streamlining were methanol: 40- 50% v/v, pH: 3.5-4.5 and flow rate:0.3-0.5ml/min. Results: Ideal conditions decided for assay were methanol, acetonitrile, pH 3.5±0.5 balanced with the diluted orthophosphoric acid solution and flow rate of 0.484ml/min and pH 3.946. Peak area ratio of the analyte was utilized for the evaluation of pharmaceutical formulation tests. Total chromatographic analysis time per sample was approximately 4.33 min with metformin and sitagliptin eluting with retention times of 3.3 and 4.4 min respectively. The optimized assay circumstance was validated as per ICH guidelines and applied for the quantitative analysis of marketed tablets containing sitagliptin and metformin. Conclusion: The validation study upheld the determination of the assay conditions by affirming that the assay was specific, accurate and linear, precise and robust. Therefore, this RP-HPLC method can be used as a routine quality control analysis of gliptin derivative like sitagliptin in combination with metformin.