title: Spatial Quantitation of Drugs in tissues using Liquid Extraction Surface Analysis Mass Spectrometry Imaging.
abstract: Liquid extraction surface analysis mass spectrometry imaging (LESA-MSI) has been shown to be an effective tissue profiling and imaging technique, producing robust and reliable qualitative distribution images of an analyte or analytes in tissue sections. Here, we expand the use of LESA-MSI beyond qualitative analysis to a quantitative analytical technique by employing a mimetic tissue model previously shown to be applicable for MALDI-MSI quantitation. Liver homogenate was used to generate a viable and molecularly relevant control matrix for spiked drug standards which can be frozen, sectioned and subsequently analyzed for the generation of calibration curves to quantify unknown tissue section samples. The effects of extraction solvent composition, tissue thickness and solvent/tissue contact time were explored prior to any quantitative studies in order to optimize the LESA-MSI method across several different chemical entities. The use of a internal standard to normalize regional differences in ionization response across tissue sections was also investigated. Data are presented comparing quantitative results generated by LESA-MSI to LC-MS/MS. Subsequent analysis of adjacent tissue sections using DESI-MSI is also reported.
authors.affiliation: Drug Safety &Metabolism, AstraZeneca R&D, Cambridge Science Park, Cambridge, CB4 0WG, UK.|Biomolecular Sciences Research Centre, Sheffield Hallam University, Howard Street, Sheffield S1 1WB, UK.
authors.forename: John G
authors.initials: JG
authors.lastname: Swales
authors.affiliation: Drug Safety &Metabolism, AstraZeneca R&D, Cambridge Science Park, Cambridge, CB4 0WG, UK.
authors.forename: Nicole
authors.initials: N
authors.lastname: Strittmatter
authors.affiliation: Drug Safety &Metabolism, AstraZeneca R&D, Cambridge Science Park, Cambridge, CB4 0WG, UK.
authors.forename: James W
authors.initials: JW
authors.lastname: Tucker
authors.affiliation: Biomolecular Sciences Research Centre, Sheffield Hallam University, Howard Street, Sheffield S1 1WB, UK.
authors.forename: Malcolm R
authors.initials: MR
authors.lastname: Clench
authors.affiliation: Drug Safety &Metabolism, AstraZeneca R&D, Cambridge Science Park, Cambridge, CB4 0WG, UK.
authors.forename: Peter J H
authors.initials: PJH
authors.lastname: Webborn
authors.affiliation: Drug Safety &Metabolism, AstraZeneca R&D, Cambridge Science Park, Cambridge, CB4 0WG, UK.
authors.forename: Richard J A
authors.initials: RJA
authors.lastname: Goodwin
mesh_terms: D000818:Animals; D002138:Calibration; D002853:Chromatography, Liquid / Q000379:methods*; D021621:Imaging, Three-Dimensional; D057230:Limit of Detection; D008297:Male; D009928:Organ Specificity; D004364:Pharmaceutical Preparations / Q000032:analysis*; D017208:Rats, Wistar; D012015:Reference Standards; D021241:Spectrometry, Mass, Electrospray Ionization; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods*; D053719:Tandem Mass Spectrometry
chemical_list: D004364:Pharmaceutical Preparations