Addressing the analytical throughput challenges in ADME screening using rapid ultra-performance liquid chromatography/tandem mass spectrometry methodologies.
High-throughput ADME screening for compound drug development properties has become an essential part of the modern drug discovery process, allowing more informed decisions to be made on the best compounds to take forward in the discovery/development process. This however is a time-consuming process requiring multiple tests to be performed, demanding a significant amount of liquid chromatography/mass spectrometry (LC/MS) instrument time. This article focuses on the use of sub-2 microm porous particle LC coupled to tandem quadrupole MS/MS mass spectrometry for the rapid screening of ADME properties. Using this approach analysis times from 30 s to 1 min were achievable allowing analysis times to be cut by 80%. The use of the small particles coupled to high flow rates allowed for sufficient resolution, even with very short analysis time, to resolve the analytes of interest from similar compounds that would interfere with the assay. The use of dedicated, intelligent, software packages allowed for the user-free generation of MS/MS conditions and the processing of the data.
Waters Corporation, Milford, MA, USA. rob_plumb@waters.com
Robert S
RS
Plumb
Warren B
WB
Potts
Paul D
PD
Rainville
Peter G
PG
Alden
Darcy H
DH
Shave
Geneen
G
Baynham
Jeffery R
JR
Mazzeo
D000818:Animals; D002853:Chromatography, Liquid / Q000379:methods*; D004353:Drug Evaluation, Preclinical; D006801:Humans; D006863:Hydrogen-Ion Concentration; D013058:Mass Spectrometry / Q000379:methods; D004364:Pharmaceutical Preparations / Q000032:analysis* / Q000378:metabolism*; D012984:Software; D012995:Solubility; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D053719:Tandem Mass Spectrometry / Q000379:methods*; D013997:Time Factors
D004364:Pharmaceutical Preparations