Analysis of a novel antiinflammatory agent, 1-(7-tert.-butyl-2,3-dihydro-3,3-dimethylbenzo[b]furan-5-yl)-4- cyclopylbutan-1-one (PGV-20229), in plasma matrices by stable-isotope-dilution gas chromatography-mass spectrometry.
A sensitive and selective GC-MS method was developed for the determination of low levels of a novel antiinflammatory agent, 1-(7-tert.-butyl-2,3-dihydro-3,3-dimethylbenzo[b]furan-5-yl)-4- cyclopropylbutan-1-one (I), in small volumes of animal plasma. The method involved the addition of 13C6-labeled-I to plasma samples, followed by a simple liquid-liquid extraction with hexane to isolate the analytes from matrix components. The levels of I in the sample extracts were determined by isotope-dilution GC-MS analysis using selected-ion monitoring. The method was linear over three orders of magnitude, with a limit of quantitation of 1.8 ng/ml I, using plasma sample volumes of 0.1 ml. The method was utilized to determine the pharmacokinetic parameters of I in rats and dogs, following intravenous administration.
Knight
P M
PM
Procter & Gamble Pharmaceuticals, Health Care Research Center, Mason, OH 45040, USA.
Scherz
M W
MW
Cruze
C A
CA
Wehmeyer
K R
KR
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000097:blood* / Q000493:pharmacokinetics; D001572:Benzofurans / Q000097:blood* / Q000493:pharmacokinetics; D002247:Carbon Isotopes; D004285:Dogs; D004355:Drug Stability; D008401:Gas Chromatography-Mass Spectrometry; D007201:Indicator Dilution Techniques; D008297:Male; D010636:Phenols / Q000097:blood* / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012680:Sensitivity and Specificity
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001572:Benzofurans; D002247:Carbon Isotopes; C110060:PGV 20229; D010636:Phenols