Chemometric-Based AQbD and Green Chemistry Approaches to Chromatographic Analysis of Remogliflozin Etabonate and Vildagliptin.

BACKGROUND

According to the green chemistry approach, during method development, the usage of toxic and carcinogenic organic solvents should be avoided or minimized for the safety of the environment and analysts. The chromatographic methods such as reverse-phase high-pressure liquid chromatography (RP-HPLC) and high-performance thin-layer chromatography (HPTLC) include the usage of class 2 organic solvents as per the International Council for Harmonization (ICH) Q3C (R6) guideline. The chromatographic analysis by HPTLC requires less organic solvent compared to the RP-HPLC method.

OBJECTIVE

Hence, HPTLC-based chromatographic analysis of vildagliptin (VIL) and remogliflozin etabonate (RMG) has been carried out using green chemistry and analytical quality by design (AQbD) approaches.

METHOD: The principal component analysis (PCA)-based chemometric analysis was applied for the identification of critical method variables (CMV) for the development of the method. The design of experiments (DoE)-based Box-Behnken design (BBD) was applied for response surface modeling (RSM) and optimization of CMV. The analytical design space (ADS) and analytical control point were navigated for the development of the HPTLC method as per the quality target analytical profile.

RESULTS

The chromatographic analysis of VIL and RMG was carried out using silica gel G60 F254 as the stationary phase and acetone-ethyl acetate-water-triethylamine (7.0 + 2.5 + 0.3 + 0.2, v/v) as the mobile phase. The HPTLC method was validated as per the ICH Q2 (R1) guideline. The HPTLC method was applied for the assay of fixed-dose combinations (FDCs) of VIL and RMG, and the results were found to comply with their labeled claim.

CONCLUSIONS

The developed method included the usage of organic solvents that belong to the class 3 category as per the ICH Q3C (R6) guideline. Hence, the developed method can be used as an eco-friendly alternative to published chromatographic methods for quality control and routine analysis of FDCs of VIL and RMG in the pharmaceutical industry.

HIGHLIGHTS: Chromatographic analysis of VIL and RMG using green chemistry and AQbD approaches. Application of the method for assay of drugs in their combined pharmaceutical dosage forms.