Metabolism of FPP-3, an anti-inflammatory propenone compound, in rat by liquid chromatography-electrospray ionization tandem mass spectrometry.
1-Furan-2-yl-3-pyridin-2-yl-propenone (FPP-3) is an anti-inflammatory agent with a propenone moiety. Following a single intravenous injection of male Sprague-Dawley rats with 4 mg/kg of FPP-3, three different metabolites of FPP-3 were identified as M1 (1-furan-2-yl-3-pyridin-2-yl-propan-1-one), M2 (1-furan-2-yl-3-pyridin-2-yl-propan-1-ol) and M3 (a glucuronide conjugate of M2) in rat urine by a liquid chromatography-electrospray tandem mass spectrometry. The structures of M1 and M2 were the same as observed previously following the incubation of rat liver microsomes with FPP-3 in the presence of NADPH. Although all metabolites of FPP-3 were identified in rat urine, only M1 and M2 were observed in the bile and feces. In addition, FPP-3 and its metabolites were mostly excreted into the urine. The M3 was identified as a glucuronide conjugate of M2 because of the addition of 176 Da from the protonated molecular ion of M2 in MS(2) and because of the production of free M2 following an incubation of urine with beta-glucuronidase. From these studies, a possible metabolic fate of FPP-3 could be proposed in vivo.
Lee
Sang Kyu
SK
College of Pharmacy, Yeungnam University, Gyeongsan, Korea.
Jeong
Hye Gwang
HG
Lee
Eung Seok
ES
Jeong
Tae Cheon
TC
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000493:pharmacokinetics* / Q000652:urine; D001646:Bile / Q000737:chemistry; D001711:Biotransformation; D005243:Feces / Q000737:chemistry; D005663:Furans / Q000737:chemistry / Q000493:pharmacokinetics* / Q000652:urine; D007275:Injections, Intravenous; D008297:Male; D015394:Molecular Structure; D011407:Propane / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics / Q000652:urine; D011725:Pyridines / Q000737:chemistry / Q000493:pharmacokinetics* / Q000652:urine; D051381:Rats; D017207:Rats, Sprague-Dawley; D021241:Spectrometry, Mass, Electrospray Ionization; D053719:Tandem Mass Spectrometry
C508534:1-furan-2-yl-3-pyridin-2-yl-propenone; D000894:Anti-Inflammatory Agents, Non-Steroidal; D005663:Furans; D011725:Pyridines; D011407:Propane