Use of a variably sensitive selected reaction monitoring method to extend the linear dynamic range for quantitative high-performance liquid chromatography/tandem mass spectrometry.
A method has been devised with the capacity to extend the linear dynamic range of a triple quadrupole mass spectrometer operated in the selected reaction monitoring (SRM) mode of analysis. This extended range experiment can be realized by simultaneously acquiring variably sensitive data, via collision energy adjustment, for the same precursor-to-product ion transition within a single SRM method. While this method can be applied universally to many different study types without any detrimental effect to the analysis or throughput, it was applied herein to acquire and quantify, within a single analysis, the concentrations of GSK-A in a multiple-dose rodent study, that previously required a dilution scheme. Using this methodology, the linear dynamic range of GSK-A was increased over traditional methods by nearly two orders of magnitude, from 2.00-10,000 ng/mL to 0.500-100,000 ng/mL.
Fries
Harvey E
HE
Preclinical Drug Discovery, Cardiovascular and Urogenital Center of Excellence in Drug Discovery, GlaxoSmithKline, King of Prussia, PA 19406, USA. harvey.e.fries@gsk.com
Aiello
Mauro
M
Evans
Christopher A
CA
D000465:Algorithms; D000818:Animals; D001774:Blood Chemical Analysis / Q000379:methods*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D038362:Glycogen Synthase Kinase 3 / Q000097:blood*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*
D038362:Glycogen Synthase Kinase 3