title: Imaging MALDI MS of Dosed Brain Tissues Utilizing an Alternative Analyte Pre-extraction Approach.
abstract: Matrix-assisted laser desorption ionization (MALDI) imaging mass spectrometry has been adopted in the pharmaceutical industry as a useful tool to detect xenobiotic distribution within tissues. A unique sample preparation approach for MALDI imaging has been described here for the extraction and detection of cobimetinib and clozapine, which were previously undetectable in mouse and rat brain using a single matrix application step. Employing a combination of a buffer wash and a cyclohexane pre-extraction step prior to standard matrix application, the xenobiotics were successfully extracted and detected with an 8 to 20-fold gain in sensitivity. This alternative approach for sample preparation could serve as an advantageous option when encountering difficult to detect analytes.
authors.affiliation: Department of Drug Metabolism & Pharmacokinetics, Genentech, Inc., 1 DNA Way, South San Francisco, CA, 94080, USA.
authors.forename: Cristine M
authors.initials: CM
authors.lastname: Quiason
authors.forename: Sheerin K
authors.initials: SK
authors.lastname: Shahidi-Latham
mesh_terms: D000818:Animals; D001384:Azetidines / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics*; D001921:Brain / Q000033:anatomy & histology*; D001923:Brain Chemistry; D003024:Clozapine / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics*; D018756:GABA Antagonists / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics*; D048369:MAP Kinase Kinase 1 / Q000037:antagonists & inhibitors*; D061848:Optical Imaging / Q000379:methods; D010880:Piperidines / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics*; D017207:Rats, Sprague-Dawley; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods*
chemical_list: D001384:Azetidines; D018756:GABA Antagonists; D010880:Piperidines; D048369:MAP Kinase Kinase 1; C574276:cobimetinib; D003024:Clozapine
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