title: Validation of bioanalytical LC-MS/MS assays: evaluation of matrix effects.
abstract: Liquid chromatography coupled to atmospheric pressure ionization tandem mass spectrometry is currently the method of choice for the quantitative determination of drugs in biological matrices. The advantages of this technique include high specificity, sensitivity and throughput. However, co-eluting matrix components, which are not observed in the chromatogram, can have a detrimental effect on the analysis, since they can cause ion suppression or enhancement of the analyte. The evaluation of matrix effects on the quantitative analysis of drugs in biological fluids is an important and sometimes overlooked aspect of assay validation. In this review, the influence of matrix effects on bioanalytical LC-MS/MS methods is discussed and illustrated with some examples. In addition, possible solutions to reduce or eliminate matrix effects are highlighted. A literature overview of validated LC-MS/MS methods published from January till June 2008 is also included. Although matrix effects are investigated in most papers, there is no consensus on how matrix effects should be evaluated during method validation. In addition, the definition of specificity should be changed for LC-MS/MS based methods.
authors.affiliation: Vrije Universiteit Brussel, Department of Pharmaceutical Chemistry, Drug Analysis and Drug Information, Laarbeeklaan 103, 1090 Brussels, Belgium.
authors.forename: Ann
authors.initials: A
authors.lastname: Van Eeckhaut
authors.forename: Katrien
authors.initials: K
authors.lastname: Lanckmans
authors.forename: Sophie
authors.initials: S
authors.lastname: Sarre
authors.forename: Ilse
authors.initials: I
authors.lastname: Smolders
authors.forename: Yvette
authors.initials: Y
authors.lastname: Michotte
mesh_terms: D000818:Animals; D002853:Chromatography, Liquid / Q000295:instrumentation* / Q000379:methods* / Q000592:standards; D017408:Guidelines as Topic; D006801:Humans; D053719:Tandem Mass Spectrometry / Q000295:instrumentation / Q000379:methods* / Q000592:standards; D054928:Validation Studies as Topic