PT  - JOURNAL ARTICLE
AU  - D Thomassen
AU  - P G Pearson
AU  - J T Slattery
AU  - S D Nelson
TI  - Partial characterization of biliary metabolites of pulegone by tandem mass spectrometry. Detection of glucuronide, glutathione, and glutathionyl glucuronide conjugates.
DP  - 1991 Sep 01
TA  - Drug Metabolism and Disposition
PG  - 997--1003
VI  - 19
IP  - 5
4099  - http://dmd.aspetjournals.org/content/19/5/997.short
4100  - http://dmd.aspetjournals.org/content/19/5/997.full
SO  - Drug Metab Dispos1991 Sep 01; 19
AB  - The hepatotoxic monoterpene pulegone is a major constituent of the herbal abortifacient pennyroyal oil. An approximately equimolar mixture of 2H3- and 14C-labeled pulegone was administered to rats to study its phase II metabolism. Radioactive conjugates that were excreted into the bile were isolated by selective derivatization and HPLC separation, and subsequently characterized from the daughter ion mass spectra of protio- and deutero-analogs of each metabolite. The biliary metabolites characterized were glucuronide and glutathione (GSH) conjugates, accounting for approximately 3% of the radioactivity excreted in bile. The glucuronides, which were 2-fold more abundant than GSH conjugates, were mainly of hydroxylated pulegone and hydroxylated, reduced pulegone. The three GSH conjugates contained xenobiotic moieties that varied in their oxidation state; one of these was tentatively identified as the GSH conjugate of the proximate oxygenated metabolite, menthofuran. The two other GSH conjugates apparently underwent subsequent glucuronidation since novel glutathionyl glucuronide conjugates were identified that contained nonhydroxylated xenobiotic moieties. The results indicate that pulegone is bioactivated via at least three distinct pathways, each marked by a different GSH conjugate. Characterization of these conjugates represents a first step in the identification of the reactive metabolites from which they are derived.