The Degradation Chemistry of Prasugrel Hydrochloride. Part 1: Drug Substance

Abstract Prasugrel hydrochloride is the active ingredient in Effient™, a thienopyridine platelet inhibitor. An extensive study of the degradation chemistry of prasugrel hydrochloride (LY640315 hydrochloride, Table 4) has been carried out on the drug substance (Part I) and on the drug product (Part II, future paper) using a multi-dimensional approach including hydrolytic, oxidative, and photolytic stressing, computational chemistry, HPLC analysis, and structure elucidation by various spectroscopic techniques. The major degradation products formed from the drug substance under the various stress conditions have been isolated and structures unambiguously determined, and the pathways leading to these products have been proposed. Fourteen new (not previously disclosed) products were discovered and characterized, in addition to four degradation products that had been previously identified in the literature. The pathways indicate that prasugrel is susceptible to hydrolysis, autoxidation (both radical-initiated and single electron mediated), and peroxide-mediated oxidation; in solution, prasugrel is susceptible to photodegradation.