Analysis of Fixed-Dose Combination of Three Antihypertensive Drugs by a Green and Quality by Design Approach.

Abstract

This paper presents the result of a combined employment of Analytical Quality-by-Design and Green Analytical Chemistry principles for the development of a robust high-performance liquid chromatography method for simultaneous determination of fixed-dose combination of three drugs, perindopril tert-butylamine, amlodipine besylate and indapamide. Optimum conditions were achieved on ZORBAX Eclipse XDB-C18 column (150mm × 4.6mm, 5μm particle size), the mobile phase comprising acetonitrile and phosphate buffer (30mM, pH2.7) in the ratio 34:66 (v/v), the flow rate of 1mLmin-1, injection volume of 10μL and UV detection at 210nm. By assigning the design space from the overlay plot, the regions within which the robustness of the method is achieved were defined and confirmed by Dong's algorithm calculations. The proposed method was validated and shown to be applicable for the determination of the three drugs in commercially available tablets. In addition, the impact of the method on the environment was assessed through four different analytical tools: National Environmental Methods Index, Analytical Eco-Scale, Green Analytical Procedure Index and Assessment of Green Profile. The proposed method was determined to be greener, with minimal impact on the environment with regard to waste production, energy consumption and use of hazardous chemicals.