Rapid pharmacokinetic screening for the selection of new drug discovery candidates using a generic isocratic liquid chromatography--atmospheric pressure ionization tandem mass spectrometry method.
A generic isocratic HPLC-APCI-MS-MS method has been developed for the determination of plasma concentrations of bioactive compounds for the selection of potential new drug discovery candidates. A 4.6 x 50 mm cyano phase column eluted with an acetonitrile/water mobile phase containing 20 mM ammonium acetate and 0.4% TFA produces retention times of 1 min or less for a wide range of compounds. This is a great advantage in new drug discovery where many compounds are analyzed once and eliminated. No time is consumed developing chromatographic conditions for each new compound. The mass spectrometer can be optimized and the samples can be processed and analyzed, all in the same day. Multiple assays can be run consecutively without changing the column or mobile phase between assays.
Colwell
Lawrence F
LF
Department of Basic Chemistry, Merck Research Laboratories, RY800B-206, P.O. Box 2000, Rahway, NJ 07065, USA.
Tamvakopoulos
Constantin S
CS
Wang
Pei Ran
PR
Pivnichny
James V
JV
Shih
Thomas L
TL
D001274:Atmospheric Pressure; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods*; D004364:Pharmaceutical Preparations / Q000097:blood*; D010599:Pharmacokinetics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013449:Sulfonamides / Q000097:blood; D013777:Tetrazoles / Q000097:blood
D004364:Pharmaceutical Preparations; D013449:Sulfonamides; D013777:Tetrazoles; C120629:L 770644