Quantitative screening and matrix effect studies of drug discovery compounds in monkey plasma using fast-gradient liquid chromatography/tandem mass spectrometry.
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.
Hsieh
Y
Y
Drug Metabolism and Pharmacokinetics Department, Schering Plough Research Institute, Kenilworth, NJ 07033, USA.
Chintala
M
M
Mei
H
H
Agans
J
J
Brisson
J M
JM
Ng
K
K
Korfmacher
W A
WA
D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003505:Cyclodextrins; D000882:Haplorhini; D013058:Mass Spectrometry / Q000379:methods; D008747:Methylcellulose; D004364:Pharmaceutical Preparations / Q000097:blood*; D012997:Solvents; D047392:beta-Cyclodextrins
D003505:Cyclodextrins; D004364:Pharmaceutical Preparations; D012997:Solvents; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D008747:Methylcellulose