Mometasone furoate (MF) is a synthetic glucocorticoid with anti-inflammatory activity, which is used for the treatment of topical skin disorders, allergic rhinitis and treatment of mild to moderate persistent asthma. The focus of this study is to examine the stability of MF in simulated lung fluid (SLF) and to clearly identify the structure of the degradation products of MF by MS and NMR analysis. Mometasone furoate degradation leads to the formation of two products, D1 and D2 with significant pH dependence. The half-lives for the conversion of MF to D1 and subsequent conversion of D1 to D2 at 37 degrees C in SLF were 1.3 and 4.8 h respectively. LC-MS and NMR analysis confirmed that D1 is 9,11-epoxide mometasone furoate while D2 represents a new chemical structure that shows cyclization within the C17-C21 region. The biological activity of these degradation products was assessed in rat lung glucocorticoid receptor binding studies. D1 showed 4 fold greater receptor affinity to glucocorticoid receptors compared to dexamethasone. However, the receptor affinity for D2 was a log order lower than that for dexamethasone. The instability of MF in SLF resulted in two degradation products, one of the degradation products showing glucocorticoid receptor activity, the other representing a new cyclized structure whose pharmacological properties have not been described. The biological significance of these degradation products is unknown.