Kinetic Study on the Isomerization of Perindopril by HPLC

Abstract

The isomerization of perindopril has been investigated using dynamics chromatography and an unified equation introduced by Trapp that was based on stochastic and theoretical plate models to determine the energies. The isomerization rate constants and Gibbs activation energies of isomerization are directly calculated from chromatographic peak parameters, i.e., retention times of the inter-converting species, peak width at half height, and relative plateau height. From the rate constant \( k_{1}^{ue} (T) \), measured at variable temperatures, the kinetic eyring activation parameters ΔG#, ΔH# and ΔS# of isomerization of perindopril were obtained. By variation of the flow rate of the mobile phase, the expected independence of the isomerization barrier from the chromatographic time scale was demonstrated for the first time. The relationships between peak shape and chromatographic conditions, such as flow rate, temperature, pH, organic modifier, and β-cyclodextrin, such as an additive, were investigated. In addition, an NMR investigation on perindopril was described.