title: Study of the forced degradation behavior of prasugrel hydrochloride by liquid chromatography with mass spectrometry and liquid chromatography with NMR detection and prediction of the toxicity of the characterized degradation products.
abstract: Prasugrel was subjected to forced degradation studies under conditions of hydrolysis (acid, base, and neutral), photolysis, oxidation, and thermal stress. The drug showed liability in hydrolytic as well as oxidative conditions, resulting in a total of four degradation products. In order to characterize the latter, initially mass fragmentation pathway of the drug was established with the help of mass spectrometry/time-of-flight, multiple stage mass spectrometry and hydrogen/deuterium exchange data. The degradation products were then separated on a C18 column using a stability-indicating volatile buffer method, which was later extended to liquid chromatography-mass spectrometry studies. The latter highlighted that three degradation products had the same molecular mass, while one was different. To characterize all, their mass fragmentation pathways were established in the same manner as the drug. Subsequently, liquid chromatography-nuclear magnetic resonance (NMR) spectroscopy data were collected. Proton and correlation liquid chromatography with NMR spectroscopy studies highlighted existence of diastereomeric behavior in one pair of degradation products. Lastly, toxicity prediction by computer-assisted technology (TOPKAT) and deductive estimation of risk from existing knowledge (DEREK) software were employed to assess in silico toxicity of the characterized degradation products.
authors.affiliation: Biocon-BMS R&D Centre (BBRC), Biocon Park, Bangalore, India.
authors.forename: Dilip Kumar
authors.initials: DK
authors.lastname: Singh
authors.affiliation: Department of Pharmaceutical Analysis, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar, Punjab, India.
authors.forename: Archana
authors.initials: A
authors.lastname: Sahu
authors.affiliation: Biocon-BMS R&D Centre (BBRC), Biocon Park, Bangalore, India.
authors.forename: Tarun
authors.initials: T
authors.lastname: Handa
authors.affiliation: Biocon-BMS R&D Centre (BBRC), Biocon Park, Bangalore, India.
authors.forename: Mallikarjun
authors.initials: M
authors.lastname: Narayanam
authors.affiliation: Department of Pharmaceutical Analysis, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar, Punjab, India.
authors.forename: Saranjit
authors.initials: S
authors.lastname: Singh
mesh_terms: D002623:Chemistry Techniques, Analytical; D002626:Chemistry, Pharmaceutical / Q000379:methods; D002851:Chromatography, High Pressure Liquid; D002853:Chromatography, Liquid / Q000379:methods*; D004355:Drug Stability; D006358:Hot Temperature; D006868:Hydrolysis; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D013058:Mass Spectrometry / Q000379:methods*; D010084:Oxidation-Reduction; D010100:Oxygen / Q000737:chemistry; D010316:Particle Size; D010782:Photolysis; D000068799:Prasugrel Hydrochloride / Q000032:analysis / Q000737:chemistry*; D012984:Software; D013696:Temperature
chemical_list: D000068799:Prasugrel Hydrochloride; D010100:Oxygen
keywords: Degradation products; In silico toxicity; Mass spectrometry; Nuclear magnetic resonance spectroscopy; Prasugrel hydrochloride