Metabolism of 4-hydroxyanisole: identification of major urinary excretory products.
The human metabolism of 4-hydroxyanisole was investigated by the analysis of urine samples from melanoma patients treated with this substance. The samples were hydrolyzed with glucoronidase and/or arylsulphatase, extracted with ethyl acetate, and, after derivatization with pentafluoropropionylanhydride, analyzed by gas chromatography-mass spectrometry. We were able to identify peaks by their retention times and mass spectra corresponding to 4-hydroxyanisole, 3,4-dihydroxyanisole, and two of its o-methyl derivatives, namely, 3-hydroxy-4-methoxy- and 4-hydroxy-3-methoxyanisole. We also detected a peak of hydroquinone, which may have originated (at least partly) from 4-hydroxyanisole. All the above-mentioned compounds were excreted predominantly as sulphates and glucuronides. Only a small proportion of the substances was present in urine in an unconjugated form. Our results demonstrate that 3,4-dihydroxyanisole is the most important metabolite of 4-hydroxyanisole.
Pavel
S
S
Department of Dermatology, Academic Medical Center, Amsterdam, The Netherlands.
Holden
J L
JL
Riley
P A
PA
D000840:Anisoles / Q000378:metabolism / Q000627:therapeutic use / Q000652:urine*; D000970:Antineoplastic Agents / Q000652:urine*; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D013058:Mass Spectrometry; D008545:Melanoma / Q000188:drug therapy / Q000652:urine*; D009364:Neoplasm Recurrence, Local; D012878:Skin Neoplasms / Q000188:drug therapy / Q000652:urine*
D000840:Anisoles; D000970:Antineoplastic Agents; C009760:mequinol