Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
7689915 | TrAC Trends in Analytical Chemistry | 2014 | 17 Pages |
Abstract
This review emphasizes the benefits of ultra-high-pressure liquid chromatography (UHPLC) in the context of in-vitro drug-metabolism and pharmacokinetics (DMPK) studies. The analysis throughput afforded by UHPLC is particularly useful during the early DMPK stages, when rapid, reliable data must be generated on a large number of new chemical entities (NCEs) to select the most appropriate drug candidates. UHPLC also offers high chromatographic resolution, an important feature for the identification of unknown metabolites that are potentially generated from NCEs by a few dozen biochemical enzymes and combinations of them. Most DMPK studies require selectivity and peak-assignment certainty that is only afforded by mass spectrometry (MS) detectors. We therefore thoroughly discuss the use of UHPLC-MS and UHPLC-tandem MS with regard to DMPK, highlighting the coupling of UHPLC with quadrupole-based MS analyzers, time-of-flight MS analyzers and hybrid analyzers.
Keywords
NCEquadrupole/time-of-flightQqTOFRPLCLTQ-OrbitrapUHPLC-MSDMPKSULTPDREDDITOFUHPLCADMETGSTGSHUGTICPCyPADCAPCIESISRMTDCKCNMS/MSUDP-glucuronosyltransferasesdrug-drug interactionMetabolic stabilityabsorption, distribution, metabolism, excretion and toxicityDwell timeTime-of-Flight SulfotransferasesCytochrome P450SIMMetabolite identificationi.d.Mass spectrometryMass spectrometry (MS)Tandem mass spectrometryInternal Diameteranalog-to-digital converterTime-to-Digital ConverterReactive metabolitedrug metabolism and pharmacokineticsnew chemical entityselected reaction monitoringselected ion monitoringHILICpotassium cyanideMetabolite profilingInductively-coupled plasmahydrophilic interaction chromatographyReversed-phase liquid chromatographyUltra-high-pressure liquid chromatographyhigh-performance liquid chromatographyHPLCGlutathioneglutathione S-transferaseelectrospray ionizationatmospheric pressure chemical ionization
Related Topics
Physical Sciences and Engineering
Chemistry
Analytical Chemistry
Authors
Dany Spaggiari, Laurent Geiser, Serge Rudaz,