Identification of photodegradants of droloxifene by combined HPLC--MS, NMR spectroscopy and computational chemistry

Abstract

A combination of high-performance liquid chromatography (HPLC)-mass spectrometry and 1 H and 13 C NMR spectroscopy was utilized to characterize the photodecay products of droloxifene, a potent new estrogen receptor agonist. Structurally similar to tamoxifen, droloxifene demonstrates a complex and unique decay scheme, including the formation of two naphthalene derivatives which were unexpected decay products and previously unreported for this class of compound. Elucidation of the decay products was assisted by the use of computational chemistry, namely by correlating simulated UV spectra and aqueous solvation free energies with actual UV spectra and HPLC retention data. In addition to describing the photodecay scheme of droloxifene, the present work demonstrates the utility of computational chemistry in providing support for the identification of unknown compounds.