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In vivo pharmacokinetic screening in cassette dosing experiments: the use of on‐line prospekt® liquid chromatography/atmospheric pressure chemical ionization tandem mass spectrometry technology in drug discovery
Author(s) -
Beaudry Francis,
Yves Le Blanc J. C.,
Coutu Michel,
Brown Nigel K.
Publication year - 1998
Publication title -
rapid communications in mass spectrometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.528
H-Index - 136
eISSN - 1097-0231
pISSN - 0951-4198
DOI - 10.1002/(sici)1097-0231(19980915)12:17<1216::aid-rcm304>3.0.co;2-o
Subject(s) - chemistry , analyte , bioanalysis , chromatography , atmospheric pressure chemical ionization , mass spectrometry , pharmacokinetics , tandem mass spectrometry , detection limit , liquid chromatography–mass spectrometry , drug discovery , tandem , analytical chemistry (journal) , ionization , chemical ionization , pharmacology , medicine , ion , organic chemistry , biochemistry , materials science , composite material
Drug discovery is a fast growing field and the number of compounds generated daily by the pharmaceutical industry is enormous. The necessity of developing new experimental strategies and analytical methods to rapidly screen the pharmacokinetics (PK) behavior of these compounds becomes a real challenge. A novel strategy to support in vivo PK screening in cassette dosing experiments, using a fully automated system capable of analyzing between 320 to 960 samples a day by instrument in a n ‐in‐one experiment ( n = 64 in this work), has been developed. Using an on‐line extraction technique, the average observed recovery was 64% using a simple C 18 procedure. A weighted (1/ x ) linear equation was used to perform standard calibration (0.5 to 500 ng/mL) and the average R value obtained was 0.994 ( R 2 = 0.997) for 63 analytes. The limit of detection, defined as a signal‐to‐noise ratio of 3 or greater, was found to be 25 pg for 41 of the 63 analytes (65%) and 250 pg for 57 of the 63 analytes (90%). The complete automation procedure using the Prospekt‐LC‐APCI/MS/MS system has substantially improved throughput in the area of drug discovery and bioanalysis. © 1998 John Wiley & Sons, Ltd.