On-line turbulent-flow chromatography-high-performance liquid chromatography-mass spectrometry for fast sample preparation and quantitation.
A sensitive and selective liquid chromatography-mass spectrometry method has been developed for the simultaneous identification and quantitation of drug substances and metabolites in rat plasma. The method combines on-line turbulent-flow chromatography, high-performance liquid chromatography and mass spectrometry. This combination is considered to be a new approach suitable for fast bio-analysis in drug discovery. Dextromethorphan, and its two metabolites, dextrorphan and 3-methoxymorphinan served as model substances. The analytes present in plasma were collected on a Cyclone column using turbulent-flow chromatography and were subsequently transferred on-line to and focused on an X-Terra MS C8 column. The analytes were eluted by a linear gradient and detected by a fast scanning mass spectrometer. The detector response was quadratic and the dynamic range was estimated to be 0.5-100 ng/ml plasma or 12.5 pg to 2.50 ng injected into the system.
Ynddal
Lars
L
Department of Drug Metabolism, Research and Development, Novo Nordisk A/S, Novo Nordisk Park, DK-2760 Maaloev, Denmark. lyn@novonordisk.com
Hansen
Steen Honoré
SH
D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D003915:Dextromethorphan / Q000097:blood; D051381:Rats; D012015:Reference Standards; D012680:Sensitivity and Specificity
D003915:Dextromethorphan