SIMULTANEOUS DETERMINATION OF ENALAPRIL, FELODIPINE AND THEIR DEGRADATION PRODUCTS IN THE DOSAGE FORMULATION BY REVERSED-PHASE HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY USING A SPHERISORB C-8 COLUMN

A reversed-phase high-performance liquid chromatographic (RP-HPLC) met hod was developed and validated for the simultaneous determination of enalapril and its two degradation products, enalaprilat (diacid, hydro lytic degradation product of enalapril) and enalapril-DKP (cyclization of enalapril); and felodipine and its degradation product, H152/37 (o xidation of felodipine) in the combined enalapril/felodipine (5 mg/5 m g) formulation. Using a Spherisorb C-8 column with a CH3CN-0.001 M KH2 PO4 (pH 2) (35:65, v/v) mobile phase, these compounds were well separa ted from each other, and also from maleic acid and the excipients in t he formulation. The method was demonstrated to be precise, accurate, s pecific and robust. Optimization of the separation in terms of mobile phase composition is crucial to the method development, which is discu ssed in detail. It is proposed that under the experimental conditions used, the retention of felodipine, DW and H152/37 is governed by the r eversed-phase partitioning process whereas that of enalapril and diaci d is governed by both the partitioning and the cation-exchange process with residual silanols.