Embracing green chromatography principles in perindopril, amlodipine and indapamide drug mixture analysis using β-cyclodextrin modified mobile phase

Abstract

Raising the level of environmental awareness in the field of liquid chromatography is considered indispensable while the use of β-cyclodextrin in a mobile phase is promising strategy in this regard. This study presents a method development in lined with ICH Q14 regulatory requirements for introducing sustainability and method life-cycle management to separate components of a cardiovascular multi-drug tablet formulation. At the beginning, the analytical method target profile was defined, separation of perindopril, amlodipine, and indapamide in a shortest possible analytical run time. Following risk analysis pointed out that the mobile phase constituents represent the critical method parameters affecting the chromatographic analyses. Design of experiments methodology and Desirability function calculation was employed to simultaneously optimize the levels of concentration of β-cyclodextrin solution, pH value and acetonitrile content in the mobile phase investigated in the ranges 5-15 mM, 4.0-6.0 and 20-30% (v/v), respectively. The optimal chromatographic conditions consisted of 10 mM β-cyclodextrin (pH 5.4) and acetonitrile in the ratio 70:30 (v/v), 2 mL min^-1 flow rate, RP-18e column kept at 25 °C, 215 nm detection wavelength, and 10 μL injection volume. The eco-friendliness of the method was assessed using the AGREE tool indicating a green and sustainable method was successfully developed.