Identification of tamoxifen metabolites in human Hep G2 cell line, human liver homogenate, and patients on long-term therapy for breast cancer.
Identification of tamoxifen metabolites in human Hep G2 cell line, human liver homogenate, and patients on long-term therapy for breast cancer.
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人 Hep G2 细胞系、人肝匀浆以及接受乳腺癌长期治疗的患者中他莫昔芬代谢物的鉴定。
DOI：
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发表时间：
1995
影响因子：
3.9
通讯作者：
R. Mccague
中科院分区：
文献类型：
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作者：
G. K. Poon;B. Walter;P. Lønning;M. N. Horton;R. Mccague
通过LC/电喷雾电离/MS检查了人肝匀浆和人Hep G2细胞系制剂中他莫昔芬的代谢。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）。将他莫昔芬与人Hep G2细胞系孵育后，在样品中观察到代谢产物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> 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。
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.