LC–MS/MS studies of ritonavir and its forced degradation products

• Published in: Journal of pharmaceutical and biomedical analysis Vol. 53; no. 4; pp. 833 - 842
• Main Authors: Rao, R. Nageswara, Ramachandra, B., Vali, R. Mastan, Raju, S. Satyanarayana
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 01.12.2010; Elsevier
• Subjects: Analysis; Analytical, structural and metabolic biochemistry; Antiretroviral; Biological and medical sciences; Chromatography, High Pressure Liquid - methods; Chromatography, Liquid - methods; Drug Stability; Forced degradation; Fragment ions; Fundamental and applied biological sciences. Psychology; General pharmacology; HIV Protease Inhibitors - analysis; HIV Protease Inhibitors - chemistry; Hydrolysis; LC–APCI–MS/MS; Medical sciences; Pharmacology. Drug treatments; Ritonavir; Ritonavir - analysis; Ritonavir - chemistry; Tandem Mass Spectrometry - methods; Antiretroviral; LC–APCI–MS/MS; Fragment ions; Ritonavir; Forced degradation; Antiretroviral agent; Enzyme; LC―APCI―MS/MS; Enzyme inhibitor; HPLC chromatography; Peptidases; Mass spectrometry MS/MS; Hydrolases; Antiviral; Degradation product; Protease inhibitor
• ISSN: 0731-7085; 1873-264X
• DOI: 10.1016/j.jpba.2010.06.004

Forced degradation of ritonavir (RTV), under the conditions of hydrolysis (acidic, basic and neutral), oxidation, photolysis and thermal stress as prescribed by ICH was studied using LC–MS/MS. Eight degradation products were formed and their separation was accomplished on Waters XTerra ® C 18 column (250 mm × 4.6 mm i.d., 5 μm) using water:methanol:acetonitrile as (40:20:40, v/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 pathways of decomposition were proposed. No previous reports were found in the literature regarding the characterization of degradation products of ritonavir.