Comparison of AQbD and grid point search methodology in the development of micellar HPLC method for the analysis of cilazapril and hydrochlorothiazide dosage form stability

Abstract

The development of stability-indicating method with isocratic elution mode based on micellar liquid chromatography for the analysis of cilazapril, hydrochlorothiazide and their degradation products was the primary aim of the present research. Since this could be done using different methodologies, two approaches were selected and comprehensively compared. The first one was risk based quality by design concept adopted by many analysts since it ensures development of robust analytical methods. The second one was multicriteria decision making approach currently interpreted in a form of experimental design complemented with grid point search is well established over past decades as a very useful way to govern analytical method development. Major drawback of later approach, related to method robustness evaluation, was discounted through proposition of simple and efficient computational procedure. Both methodologies ultimately resulted in successful chromatographic separations of all investigated substances which included analysis on XTerra RP 18 (3.9 × 150 mm, 5 μm) column with temperature set at 30 °C, mobile phase consisting of acetonitrile and Brij L23 aqueous solution (18 mmol L−1, pH 3.8) in ratio 13:87 (%, v/v) pumped at 1 mL min−1 flow rate while UV detection was performed at 215 nm. Both the 3D representation of a design space as well as grid obtained with later approach pointed out that the method performance criteria would not be compromised when amount of acetonitrile amount varies in range 12–14% (v/v), pH of the water phase in range 3.4–4.0, while concentration of Brij L23 aqueous solution can be within 15–20 mmol L−1. Hence, although the method development was based on different starting hypothesis, both methodologies enabled achievement of reliable and robust analytical methods that could serve in monitoring of cilazaprile and hydrochlorothiazide combined dosage form stability.