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Quantitative screening and matrix effect studies of drug discovery compounds in monkey plasma using fast‐gradient liquid chromatography/tandem mass spectrometry
Author(s) -
Hsieh Yunsheng,
Chintala Madhu,
Mei Hong,
Agans Jacqueline,
Brisson JeanMarc,
Ng Kwokei,
Korfmacher Walter A.
Publication year - 2001
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/rcm.479
Subject(s) - chemistry , chromatography , atmospheric pressure chemical ionization , high performance liquid chromatography , mass spectrometry , bioanalysis , tandem mass spectrometry , ion suppression in liquid chromatography–mass spectrometry , electrospray ionization , liquid chromatography–mass spectrometry , selected reaction monitoring , matrix (chemical analysis) , analytical chemistry (journal) , chemical ionization , ionization , ion , organic chemistry
A higher‐throughput bioanalytical method based on fast‐gradient (1 min run time) high‐performance liquid chromatography (HPLC) coupled with tandem mass spectrometry (MS/MS) was developed for screen‐type analyses of plasma samples from early drug discovery studies in support of exploratory pharmacodynamic studies. The HPLC system equipped with minibore column was interfaced with either atmospheric pressure chemical ionization (APCI) or electrospray (ESI) ionization techniques. The matrix ion suppression effect of both quantitative HPLC/MS/MS analyses was compared using the post‐column infusion system. The use of the described methods provided advantages such as a shorter chromatographic region of ion suppression, less solvent consumption and shorter run times in comparison with standard analytical column HPLC/MS/MS methods. The analytical results obtained by both HPLC/MS/MS methods were in good agreement (within 15% of error) and displayed a good correlation with the pharmacodynamic outcome. Copyright © 2001 John Wiley & Sons, Ltd.