A Novel Approach to AQbD-Assisted Green and Robust UPLC Method for the Determination of Selected Aminoquinoline Antimalarial Drugs: Assessment of Green Method

Abstract

Greening analytical procedures have gained popularity in the area of pharmaceutical industries in order to safeguard the environment. In this study, an innovative methodology by integrating analytical quality-by-design (AQbD) along with Green Chemistry concepts with a systematic approach has been used to develop an environmentally-friendly and more robust ultra performance liquid chromatography (UPLC) method for the determination of three selected aminoquinoline antimalarial drugs namely amodiaquine hydrochloride (AMD), chloroquine phosphate (CHQ) and piperaquine phosphate (PPQ). An environmentally benign solvent ethanol has been chosen as an alternative to the commonly used acetonitrile and methanol, which are widely used. Based on the comprehensive risk analysis, the critical method parameters (CMP’s) that affect the critical method attributes (CMA’s) have been identified and the final method parameters were further optimized with the help of a full factorial design and the design of experiments (DOE), established the “design space”(DS) and identified the “method-operable-design-region (MODR) for the developed method. Achieved the separation with the use of an Acquity- UPLC BEH Shield RP-18 (100 mm × 2.1 mm), 1.7 μm column by using an isocratic elution of mobile phase containing 0.1% trifluoroacetic acid in water, ethanol in a mixture of 90:10% v/v and maintained a flow rate of 0.2 mL min-1 and the column oven temperature was 40 ºC and the UV detection wavelength of 225 nm was employed. A statistical tool Analysis of Variance (ANNOVA) has been used to assess the model’s statistical significance and found that the model’s p-values is < 0.00005 and its lack of fi is > 0.05 respectively, which demonstrates that the selected model is the most appropriate predictive tool for the analyzed responses R1 & R2 (i.e. peak resolutions R1 & R2). The proposed method’s linearity, accuracy & precision studies has been successfully validated in compliance with USP <1225> and ICH Q2 (R1) guidelines. Further assessed the proposed method’s greenness using various green evaluation tools such as: “complex green analytical procedure index”-cGAPI, “analytical greenness”-AGREE, “analytical method green score”-AMGS and found acceptable results. This novel AQbD-assisted eco-friendly analytical method for the quantification of AMD, CHQ & PPQ in bulk drugs (APIs) or finished dosage forms is simple, rapid, precise and accurate, robust and environmentally benign.