title: Controlled-pH tissue cleanup protocol for signal enhancement of small molecule drugs analyzed by MALDI-MS imaging.
abstract: The limit of detection of low-molecular weight compounds in tissue sections, analyzed by matrix assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI), was significantly improved by employing sample washing using a pH-controlled buffer solution. The pH of the washing solutions were set at values whereby the target analytes would have low solubility. Washing the tissue sections in the buffered solution resulted in removal of endogenous soluble ionization-suppressing compounds and salts, while the target compound remained in situ with minor or no delocalization during the buffered washing procedure. Two pharmaceutical compounds (cimetidine and imipramine) and one new protease inhibitor compound were successfully used to evaluate the feasibility of the pH-controlled tissue washing protocol for MALDI-MSI. Enhancement in signal-to-noise ratio was achieved by a factor of up to 10.
authors.affiliation: Department of Pharmaceutical Biosciences, Medical Mass Spectrometry, Uppsala University, Uppsala, Sweden.
authors.forename: Mohammadreza
authors.initials: M
authors.lastname: Shariatgorji
authors.forename: Patrik
authors.initials: P
authors.lastname: Källback
authors.forename: Lena
authors.initials: L
authors.lastname: Gustavsson
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Schintu
authors.forename: Per
authors.initials: P
authors.lastname: Svenningsson
authors.forename: Richard J A
authors.initials: RJ
authors.lastname: Goodwin
authors.forename: Per E
authors.initials: PE
authors.lastname: Andren
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D002927:Cimetidine / Q000032:analysis / Q000302:isolation & purification; D006863:Hydrogen-Ion Concentration; D007099:Imipramine / Q000032:analysis / Q000302:isolation & purification; D008297:Male; D051379:Mice; D004364:Pharmaceutical Preparations / Q000032:analysis* / Q000302:isolation & purification; D051381:Rats; D017208:Rats, Wistar; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D004364:Pharmaceutical Preparations; D002927:Cimetidine; D007099:Imipramine