Poon G K, Walter B, Lønning P E, Horton M N, McCague R
CRC Centre for Cancer Therapeutics, Institute of Cancer Research, Sutton, Surrey, UK.
Drug Metab Dispos. 1995 Mar;23(3):377-82.
The metabolism of tamoxifen was examined in human liver homogenate and human Hep G2 cell line preparations by LC/electro spray ionization/MS. Several metabolites were detected in the human liver homogenate extracts, namely N-didesmethyltamoxifen (metabolite I), alpha-hydroxytamoxifen (metabolite II), 4-hydroxytamoxifen (metabolite III), N-desmethyltamoxifen (metabolite IV), and tamoxifen N-oxide (metabolite V). Metabolites II, III, IV, and V were observed in the samples after incubating tamoxifen with the human Hep G2 cell line. When these results were compared with the metabolic profiles in patients, apart from metabolites I-V, alpha-hydroxy-N-desmethyltamoxifen (VI) and 4-hydroxy N-desmethyltamoxifen (VII) were present in all the plasma samples. In addition, in patients who had received tamoxifen treatment daily for > 6 months, several minor metabolites were detected, namely 4-hydroxytamoxifen N-oxide (metabolite VIII) and two dihydroxylated analogs (metabolites IX and X). The precise positions of the hydroxylation have yet to be determined.
通过液相色谱/电喷雾电离/质谱法，在人肝匀浆和人肝癌Hep G2细胞系制剂中研究了他莫昔芬的代谢情况。在人肝匀浆提取物中检测到几种代谢物，即N-去二甲基他莫昔芬（代谢物I）、α-羟基他莫昔芬（代谢物II）、4-羟基他莫昔芬（代谢物III）、N-去甲基他莫昔芬（代谢物IV）和他莫昔芬N-氧化物（代谢物V）。在将他莫昔芬与人肝癌Hep G2细胞系一起孵育后的样品中观察到了代谢物II、III、IV和V。当将这些结果与患者的代谢谱进行比较时，除了代谢物I-V外，所有血浆样品中均存在α-羟基-N-去甲基他莫昔芬（VI）和4-羟基-N-去甲基他莫昔芬（VII）。此外，在每天接受他莫昔芬治疗超过6个月的患者中，检测到几种次要代谢物，即4-羟基他莫昔芬N-氧化物（代谢物VIII）和两种二羟基化类似物（代谢物IX和X）。羟基化的精确位置尚未确定。
