title: Expanding the linear dynamic range in quantitative high performance liquid chromatography/tandem mass spectrometry by the use of multiple product ions.
abstract: A strategy for expanding the linear working range in bioanalysis using quantitative high performance liquid chromatography/tandem mass spectrometry (HPLC/MS/MS) is presented. The strategy involves monitoring multiple product ions. Herein we demonstrate the strategy on a rat plasma assay for a proprietary experimental drug where the linear range is expanded from 2 to 4 orders of magnitude. A primary sensitive ion was monitored to obtain a high sensitivity range calibration curve (0.400 to 100 ng/mL) while a less sensitive secondary ion was monitored to obtain a low sensitivity range calibration curve (90.0 to 4000 ng/mL). Each calibration curve gave acceptable linearity (r >0.990). Quality control samples at low, mid and high levels within each calibration curve demonstrated acceptable precision and accuracy (within 20% for all levels). The technique was successfully applied to rat pre-clinical sample analysis.
authors.affiliation: Alcon Research, Limited, 6201 South Freeway, Fort Worth, TX, 76134-2099, USA. michael.curtis@alconlabs.com
authors.forename: M A
authors.initials: MA
authors.lastname: Curtis
authors.forename: L C
authors.initials: LC
authors.lastname: Matassa
authors.forename: R
authors.initials: R
authors.lastname: Demers
authors.forename: K
authors.initials: K
authors.lastname: Fegan
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D015507:Drugs, Investigational / Q000032:analysis* / Q000493:pharmacokinetics*; D007477:Ions / Q000097:blood*; D013058:Mass Spectrometry / Q000379:methods*; D051381:Rats; D012680:Sensitivity and Specificity
chemical_list: D015507:Drugs, Investigational; D007477:Ions