Determination of Ramipril and Its Precursors by Reverse Phase High Performance Liquid Chromatography

Abstract

A sensitive, accurate and reproducible method for the analysis of ramipril and its two precursors (precursors I and II), which could be present as impurities in bulk material or pharmaceutical preparations, has been described. A simple isocratic HPLC elution method consisting of acetonitrile: 5% phosphoric acid (30:70) was employed for the separation of ramipril from precursors I and II in 15 minutes. The limit of detection under UV 220nm for ramipril was 36 pmole ± 8.20%. A standard curve was constructed for ramipril determination. These chromatographic conditions failed to separate peaks corresponding to precursors I and II. Another mobile phase, acetonitrile: 5% phosphoric acid (20:80), allowed the separation and quantification of precursors I and II in 20 minutes. The limit of detection under UV 220 nm was 67 pmole ± 8.06% and 76 pmole ± 10.04% for precursors I and II respectively. Ramipril peak has a tendency to broaden drastically under these chromatographic conditions.