title: Matrix Effect Compensation in Small-Molecule Profiling for an LC-TOF Platform Using Multicomponent Postcolumn Infusion.
abstract: The possible presence of matrix effect is one of the main concerns in liquid chromatography-mass spectrometry (LC-MS)-driven bioanalysis due to its impact on the reliability of the obtained quantitative results. Here we propose an approach to correct for the matrix effect in LC-MS with electrospray ionization using postcolumn infusion of eight internal standards (PCI-IS). We applied this approach to a generic ultraperformance liquid chromatography-time-of-flight (UHPLC-TOF) platform developed for small-molecule profiling with a main focus on drugs. Different urine samples were spiked with 19 drugs with different physicochemical properties and analyzed in order to study matrix effect (in absolute and relative terms). Furthermore, calibration curves for each analyte were constructed and quality control samples at different concentration levels were analyzed to check the applicability of this approach in quantitative analysis. The matrix effect profiles of the PCI-ISs were different: this confirms that the matrix effect is compound-dependent, and therefore the most suitable PCI-IS has to be chosen for each analyte. Chromatograms were reconstructed using analyte and PCI-IS responses, which were used to develop an optimized method which compensates for variation in ionization efficiency. The approach presented here improved the results in terms of matrix effect dramatically. Furthermore, calibration curves of higher quality are obtained, dynamic range is enhanced, and accuracy and precision of QC samples is increased. The use of PCI-ISs is a very promising step toward an analytical platform free of matrix effect, which can make LC-MS analysis even more successful, adding a higher reliability in quantification to its intrinsic high sensitivity and selectivity.
authors.affiliation: †Division of Analytical Biosciences, Leiden Academic Centre for Drug Research, Leiden University, Einsteinweg 55, 2333CC Leiden, The Netherlands.|‡Analytical Chemistry Department, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), Sarriena s/n, 48940 Leioa, Spain.
authors.forename: Oskar
authors.initials: O
authors.lastname: González
authors.affiliation: †Division of Analytical Biosciences, Leiden Academic Centre for Drug Research, Leiden University, Einsteinweg 55, 2333CC Leiden, The Netherlands.
authors.forename: Michael
authors.initials: M
authors.lastname: van Vliet
authors.affiliation: †Division of Analytical Biosciences, Leiden Academic Centre for Drug Research, Leiden University, Einsteinweg 55, 2333CC Leiden, The Netherlands.
authors.forename: Carola W N
authors.initials: CW
authors.lastname: Damen
authors.affiliation: †Division of Analytical Biosciences, Leiden Academic Centre for Drug Research, Leiden University, Einsteinweg 55, 2333CC Leiden, The Netherlands.
authors.forename: Frans M
authors.initials: FM
authors.lastname: van der Kloet
authors.affiliation: †Division of Analytical Biosciences, Leiden Academic Centre for Drug Research, Leiden University, Einsteinweg 55, 2333CC Leiden, The Netherlands.
authors.forename: Rob J
authors.initials: RJ
authors.lastname: Vreeken
authors.affiliation: †Division of Analytical Biosciences, Leiden Academic Centre for Drug Research, Leiden University, Einsteinweg 55, 2333CC Leiden, The Netherlands.
authors.forename: Thomas
authors.initials: T
authors.lastname: Hankemeier
mesh_terms: D000082:Acetaminophen / Q000652:urine; D001562:Benzimidazoles / Q000652:urine; D001565:Benzoates / Q000652:urine; D001713:Biphenyl Compounds; D002851:Chromatography, High Pressure Liquid / Q000295:instrumentation; D002997:Clomipramine / Q000652:urine; D004095:Dihydropyridines / Q000652:urine; D004743:Enkephalin, Leucine / Q000652:urine; D006801:Humans; D013058:Mass Spectrometry / Q000295:instrumentation; D009543:Nifedipine / Q000652:urine; D004364:Pharmaceutical Preparations / Q000652:urine*; D019821:Simvastatin / Q000652:urine; D000077333:Telmisartan; D013777:Tetrazoles / Q000652:urine; D013997:Time Factors
chemical_list: D001562:Benzimidazoles; D001565:Benzoates; D001713:Biphenyl Compounds; D004095:Dihydropyridines; D004364:Pharmaceutical Preparations; D013777:Tetrazoles; C060285:lacidipine; D000082:Acetaminophen; D004743:Enkephalin, Leucine; D019821:Simvastatin; D009543:Nifedipine; D002997:Clomipramine; C081643:candesartan; D000077333:Telmisartan