Characterization of in vitro metabolites from human liver microsomes using directly coupled hplc-nmr: application to a phenoxathiin monoamine oxidase-A inhibitor.
1. The metabolism of 1-ethylphenoxathiin-10,10-dioxide (BW1370U87), an experimental compound designed as an inhibitor of monoamine oxidase-A for use as a possible anti-depression agent, has been studied in a human liver microsome preparation. 2. The identities of the metabolites have been determined using directly coupled hplc-1H nmr at 600 MHz in the stop-flow mode in this first study of in vitro xenobiotic metabolism using hplc-nmr. 3. The xenobiotic substances that were identified comprised the parent compound BW1370U87 (with -CH2CH3 at C1) together with sidechain-oxidized metabolites with C1 substituents of -CHOH.CH3, -CH2.CH2OH, -CHOH.CH2OH and -CH2.COOH, plus the unsubstituted phenoxathiin-10,10-dioxide.
Shockcor
J P
JP
Wellcome Research Laboratories, Research Triangle Park, NC 27706, USA.
Silver
I S
IS
Wurm
R M
RM
Sanderson
P N
PN
Farrant
R D
RD
Sweatman
B C
BC
Lindon
J C
JC
D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006571:Heterocyclic Compounds / Q000493:pharmacokinetics*; D006801:Humans; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008862:Microsomes, Liver / Q000737:chemistry / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000493:pharmacokinetics*; D013056:Spectrophotometry, Ultraviolet; D015262:Xenobiotics / Q000378:metabolism
D006571:Heterocyclic Compounds; D008996:Monoamine Oxidase Inhibitors; D015262:Xenobiotics; C076100:1-ethylphenoxathiin 10,10-dioxide