Stability of ramipril in the solvents of different pH.

The stability of ramipril in the buffer solution with different pH and the influence of acid, alkaline and oxidative medium on ramipril stability were studied. The ramipril degradation products were determined by high-performance liquid chromatography (HPLC) method. Acetonitrile:sodium perchlorate was used as the mobile phase, at a flow rate of 1.0 ml/min (linear gradient elution). A Nucleosil 100-S 5 microm C18, 250 mm x 4.6 mm i.d. was utilized as stationary phase. Detection was affected spectrophotometrically at 210 nm. The drug substance was dissolved in the ammonium phosphate buffer (pH 3, 5 and 8) and these solutions were stored at 90 degrees C for 1 h. The other series of test solutions were prepared from stock solution (drug substance dissolved in solvent A of the mobile phase) by dilution in acid (0.1M HCl), alkaline (0.1M NaOH) and oxidative (hydrogen peroxide solution) medium. More then 0.2% of impurity D (ramipril-diketopiperazine) was detected in the buffer of pH 3 and pH 5. In the buffer of pH 8 there was detected more then 1% of impurity E (ramipril-diacid). No peaks for degradation products appeared in the chromatograms above limit of quantification. The alkaline medium has the greatest effect on degradation of ramipril into impurity E (more than 50%).