Characterization of degradation products of mometasone furoate

Received October 29, 2003, accepted November 12, 2003Guenther Hochhaus, Ph.D., Department of Pharmaceutics, College of Pharmacy, Gainesville, FL.,32610 USAHochhaus@ufl.eduPharmazie 59: 367–373 (2004)Mometasone furoate (MF) is a synthetic glucocorticoid with anti-inflammatory activity, which is used forthe treatment of topical skin disorders, allergic rhinitis and treatment of mild to moderate persistentasthma. The focus of this study is to examine the stability of MF in simulated lung fluid (SLF) and toclearly identify the structure of the degradation products of MF by MS and NMR analysis. Mometa-sone furoate degradation leads to the formation of two products, D1 and D2 with significant pH depen-dence. The half-lives for the conversion of MF to D1 and subsequent conversion of D1 to D2 at 37 Cin SLF were 1.3 and 4.8 h respectively. LC-MS and NMR analysis confirmed that D1 is 9,11-epoxidemometasone furoate while D2 represents a new chemical structure that shows cyclization within theC17–C21 region. The biological activity of these degradation products was assessed in rat lung gluco-corticoid receptor binding studies. D1 showed 4 fold greater receptor affinity to glucocorticoid recep-tors compared to dexamethasone. However, the receptor affinity for D2 was a log order lower thanthat for dexamethasone. The instability of MF in SLF resulted in two degradation products, one of thedegradation products showing glucocorticoid receptor activity, the other representing a new cyclizedstructure whose pharmacological properties have not been described. The biological significance ofthese degradation products is unknown.1. IntroductionMometasone furoate (MF, C