Liquid chromatographic-atmospheric pressure ionization mass spectrometric analysis of toremifene metabolites in human urine

Mass spectrometric characterization of urinary toremifene metabolites for doping control analyses

“…The position of the hydroxyl group in the aromatic ring was already questioned by Watanabe et al [28]. Results obtained in this study support the alkylic nature of the hydroxyl group for M2a and this is the first time that this structure is proposed.…”

“…Metabolic pathways detected for toremifene include N-desmethylation, hydroxylation, dihydroxylation, reduction, methylation and dehalogenation and combinations of them. Some of proposed metabolic pathways (N,N-didesmethylation, N-desmethylation + hydroxylation + hydroxymethylation, hydroxy-quinine and hydroxylation + oxidation) were not detected (Table 1) despite the fact that they were previously reported for tamoxifen, clomifene and toremifene [3,4,14,[18][19][20][21]25,[28][29][30]. As it can be observed in Table 1, N-desmethylated and dehalogenated metabolites were detected mainly in free form.…”

“…Metabolic pathways studied were based on those metabolites reported in previous studies for toremifene [3,13,14,20,21,24,26,[28][29][30] and other related compounds, such as tamoxifen and clomifene [3,4,17,[31][32][33][34][35][36][37][38][39][40][41]. All previously reported metabolic pathways and their combination were included in SRM method, with the main exception of those proposed after metabolic removal of the amine function because of no ionization in positive ion mode was expected for these compounds [13][14][15][18][19][20][21][22][23][24][25]27,42] ( Table 1).…”

“…Few analytical methods for the urinary detection of toremifene administration have been developed [3,14,[26][27][28][29]. Different metabolic pathways have been described as the most characteristic for toremifene and related compounds such as tamoxifen and clomifene including, hydroxylation, N-desmethylation, N,Ndidesmethylation, deaminohydroxylation, deaminocarboxylation, N-oxide formation, among others [3,4,17,[30][31][32][33][34][35][36][37][38][39][40][41][42].…”

Pharmacokinetics of Exogenous Natural and Synthetic Estrogens and Antiestrogens

“…Up to ten toremifene metabolites were described in human feces; however, these structures were not presented (ANTTILA et al 1990). Four unconjugated and three glucuronide-conjugated metabolites were detected in human urine (WATANABE et al 1989). Droloxifene is metabolized in humans mainly by direct glucuronidation to droloxifene-glucuronide.…”