Identification of products formed during UV irradiation of tamoxifen and their use for fluorescence detection in high-performance liquid chromatography

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

“…10 Upon exposure to light, it has been shown that tamoxifen isomerizes to its corresponding geometric isomer, with each isomer capable of undergoing a cyclization reaction with a loss of two hydrogen atoms to form a corresponding phenanthrene analog. 4 A similar behavior was also expected for droloxifene.…”

“…Hence the spectral simulations, although fairly accurate in modeling the experimental spectra, could not be used to assign definitively the structures of each isomer. The UV spectra of the phenanthrenes identified from the photodecomposition of tamoxifen and its geometric isomer 4 had distinguishing characteristics which were very similar to the spectra of 4 and 5, respectively. Owing to structural similarities between droloxifene and tamoxifen, their respective phenanthrene degradants would be expected to have very similar UV spectra.…”

“…Each compound displayed a prominent absorption band between 250 and 260 nm, with the overall UV profile consistent with hydroxylated phenanthrenes 12 and those phenanthrenes derived from tamoxifen. 4 As a potentially useful first approach, the UV spectra of the three proposed phenanthrene structures were calculated through computer modeling, then compared with the actual spectra of the proposed phenanthrene compounds 2, 4 and 5. The modeling of phenanthrene structures I, II and III accurately produced spectra with !…”

“…Owing to structural similarities between droloxifene and tamoxifen, their respective phenanthrene degradants would be expected to have very similar UV spectra. In addition, the phenanthrene derived from tamoxifen is more polar than that derived from its geometric isomer based on reversedphase HPLC retention, 4 which corresponds to 4 being more polar than 5 (Fig. 2).…”

“…1,2 In the case of tamoxifen, structural identity of these phenanthrenes has been clearly made. 3,4 However, the complete photodegradation profile of droloxifene or any other triphenylethylene compound has not been formally reported. The purpose of this study was to elucidate the photodegradation pathways of droloxifene and provide identification of the degradation products therein.…”