Chemometrical Approach in Fosinopril-Sodium and its Degradation Product Fosinoprilat Analysis

Abstract

In this paper the experimental design has been applied to define the optimum chromatographic conditions for the separation of fosinopril sodium and its degradation product, fosinoprilat. Fosinopril is a prodrug and after being hydrolysed, it becomes an active drug fosinoprilat. For experimental screening full factorial design 23 was applied. Methanol content, pH of the mobile phase and column temperature were independent variables or factors to be investigated in two levels - »low« and »high«. Capacity and selectivity factors were chosen as dependent variables and matrix was applied to estimate coefficients of the linear model. After experimental screening, RSM (response surface methodology) was applied for optimization. Optimum conditions were: X Terra™ 150 mm × 4.6 mm, 5 μm particle column at 45 °C; methanol-water (75 : 25 v/v) at pH 3.1 as a mobile phase, with a flow rate of 1 mL min−1. UV detection was performed at 220 nm. Propylparaben was used as an internal standard. The proposed method is rapid, accurate, selective and because of its sensitivity and reproducibility, it may be used for the quantitative analysis of fosinopril sodium and its degradation product in Monopril® tablets. Recovery values for fosinopril sodium were between 101.6% and 102.9% and content of degradation product fosinoprilat was lower than 5%. Applying the chemometrical approach enables a relatively limited number of experiments to define factors which affect the chromatographic behavior of investigated substances and obtain optimum conditions for their analysis.