Liquid chromatography tandem mass spectrometric studies of indinavir sulphate and its forced degradation products

Indinavir sulphate was subjected to forced degradation under hydrolysis (acidic, basic and neutral), oxidation, photolysis and thermal stress as prescribed by ICH guidelines. It was degraded under acidic, basic, neutral and oxidative stress conditions, while it was stable under other conditions. After degradation total eight degradation products were formed. The degradation products were identified and their separation was accomplished on Waters XTerra® C18 column (250 mm × 4.6 mm i.d., 5 μm) using 20 mM ammonium actate:acetonitrile as (50:50, v/v) mobile phase in an isocratic elution mode by LC. The method was extended to LC–MS/MS for characterization of the degradation products and the fragmentation pathways were proposed. The proposed structures of degradation products were also confirmed by HRMS studies. No previous reports were found in the literature regarding the characterization of degradation products of indinavir sulphate.

► Development and validation of a RP-HPLC method for the separation of indinavir sulphate and its degradation products.
► Forced degradation studies were carried out as prescribed in ICH guidelines.
► Identification, characterization and probable fragmentation pathways of degradation products were proposed based on LC–MS/MS and HRMS studies.