Liquid chromatographic separation, determination and ESI-MS/MS, FT-IR and NMR characterization of the forced degradation products of cinacalcet

Abstract

A validated stability indicating RP-HPLC assay of cinacalcet was developed by separating its related substances and degradants on a Phenomenex C₈ (250 × 4.6 mm, 5 µm) column using 10 mM aqueous ammonium acetate–acetonitrile as the mobile phase in a gradient mode of elution at a flow rate of 1.0 mL min⁻¹ at 25 °C. The column effluents were monitored by a photo diode array detector set at 270 nm. The method was validated for accuracy, precision and linearity according to ICH guidelines. The limits of quantification of the impurities were in the range of 0.23–0.30 µg mL⁻¹. The forced degradation of cinacalcet was carried out under acidic, basic, thermal, photo, and peroxide conditions, and the degradation products were isolated and characterized by ESI-MS/MS, FT-IR, ¹H and ¹³C NMR spectroscopy. The method was successfully applied not only to quantify the degradation products but also to quantify process related substances of cinacalcet in bulk drugs.