title: Study of temoporfin metabolism by HPLC and electrospray mass spectrometry.
abstract: The in vivo and in vitro metabolism of temoporfin (m-THPC), one of the most potent photosensitizers for the treatment of cancer by photodynamic therapy, has been studied in detail by HPLC with fluorescence and spectrophotometric detection and on-line HPLC-electrospray mass spectrometry. The results showed that temoporfin was not metabolized in vivo and was excreted unchanged via the biliary system into the faeces. No temoporfin or metabolites were detected in the urine. In vitro incubation of temoporfin with human and rat liver microsomal preparations in the presence of NADPH resulted in no metabolite production, even after enzyme induction with cytochrome P-450 isoenzyme inducers such as phenobarbitone, dexamethasone and 3-methylcholanthrene. No conjugation of temoporfin by phase II cytosolic enzymes was observed. It is concluded that the possible 'metabolites' previously observed were artifacts generated by photochemical oxidation of temoporfin to hydroxylated derivatives during the sample administration, collection, preparation and extraction procedures or were impurities already present in the original drug before administration for metabolic studies. These have been confirmed experimentally.
authors.affiliation: MRC Toxicology Unit, Hodgkin Building, University of Leicester, P. O. Box 138, Lancaster Road, Leicester LE1 9HN, UK.
authors.forename: H
authors.initials: H
authors.lastname: Cai
authors.forename: Q
authors.initials: Q
authors.lastname: Wang
authors.forename: J
authors.initials: J
authors.lastname: Luo
authors.forename: C K
authors.initials: CK
authors.lastname: Lim
mesh_terms: D000818:Animals; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis / Q000378:metabolism; D003600:Cytosol / Q000737:chemistry / Q000378:metabolism; D004790:Enzyme Induction / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D007527:Isoenzymes / Q000096:biosynthesis / Q000378:metabolism; D013058:Mass Spectrometry; D008652:Mesoporphyrins / Q000097:blood / Q000378:metabolism*; D008862:Microsomes, Liver / Q000737:chemistry / Q000378:metabolism; D017319:Photosensitizing Agents / Q000097:blood / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: D007202:Indicators and Reagents; D007527:Isoenzymes; D008652:Mesoporphyrins; D017319:Photosensitizing Agents; D003577:Cytochrome P-450 Enzyme System; C072269:temoporfin