Analysis of tamoxifen and its metabolites in synthetic gastric fluid digests and urine samples using high-performance liquid chromatography with electrospray mass spectrometry

We report on the transformation of tamoxifen at 37 degreesC in synthetic ga stric fluid as studied by high-performance liquid chromatography with tripl e quadrupole mass spectrometry. The major transformation products detected were (E)-isomer of tamoxifen, metabolite D, and several unidentified compon ents having m/z. 404. Addition of pepsin to the gastric fluid inhibited for mation of all of these products. We analyzed several urine samples from bre ast cancer patients undergoing tamoxifen treatment. Metabolite D was identi fied in the urine samples and in the gastric fluid digest at a retention ti me of 22.0 min eluting from a reversed-phase HPLC column. Although several metabolites were found in all the urine samples of patients, some metabolit es were detected in one sample but not others, suggesting tamoxifen metabol ism varies in patients. (C) 2001 Elsevier Science B.V. All rights reserved.