title: Internal standard signal suppression by co-eluting analyte in isotope dilution LC-ESI-MS.
abstract: The suppression of the internal standard by increasing concentrations of the co-eluting analyte in calibration series and plasma samples analysed by LC-ESI-MS was studied using the isotope dilution technique. A series of three analyte/deuterated analyte pairs including fexofenadine/d6-fexofenadine, dapsone/d4-dapsone and peudoephedrine/d3-ephedrine were investigated. Suppression of the internal standard signal was noticed in extracted plasma samples containing fexofenadine and d6-fexofenadine as internal standard, as well as in solvent based calibration solutions of the three pair of compounds noted above during LC-ESI-MS analysis at flow rates greater than 100 microL min(-1). This signal suppression effect was described by invoking Enke's model of electrospray ion generation. This model suggests that signal suppression can be ascribed to the competition between ionic species for charged surface sites present on the generated droplets during the electrospray process. The slopes of the calibration curves of the three analytes were close to unity (fexofenadien/d6-fexofenadine 0.964 +/- 0.008, pseudoephedrine/d3-ephedrine 1.02 +/- 0.080 and dapsone/d4-dapsone 0.905 +/- 0.048) as predicted by the model, indicating that quantitation should not be affected by the variation in the peak area of the internal standard.
authors.affiliation: Axelson BioPharma Research Inc., 201-4606 Canada Way, Burnaby, BC, Canada V5G 1K5.
authors.forename: Luis E
authors.initials: LE
authors.lastname: Sojo
authors.forename: Gina
authors.initials: G
authors.lastname: Lum
authors.forename: Priscilla
authors.initials: P
authors.lastname: Chee
mesh_terms: D002138:Calibration; D002853:Chromatography, Liquid / Q000379:methods*; D003622:Dapsone / Q000032:analysis; D004809:Ephedrine / Q000032:analysis; D007553:Isotope Labeling; D004364:Pharmaceutical Preparations / Q000032:analysis*; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D016593:Terfenadine / Q000031:analogs & derivatives* / Q000032:analysis
chemical_list: D004364:Pharmaceutical Preparations; D016593:Terfenadine; D003622:Dapsone; C093230:fexofenadine; D004809:Ephedrine