MALDI-MSI analysis of coronal and sagittal brain sections from mice dosed intraperitoneally with CNS drugs donepezil, tacrine, clozapine, haloperidol, and aripiprazole. (A) MALDI-MSI images of mouse brain sections treated with five drugs at 150 μm lateral resolution in positive ion mode, comparing the different intensities in untreated tissue versus pretreated tissues. (B–C) The quantitative calibration curves of donepezil obtained from MALDI-MSI for untreated (R2 = 0.9641) and pretreated (R2 = 0.9916) mouse tissue sections. (D) LC – MS/MS validation of the tissue-specific distribution of donepezil in brain tissues, tissue punches collected from different brain regions used for the LC – MS/MS analyses and MALDI imaging of donepezil. A1 (cortex), A2 (hippocampus), A3 (thalamus), A4 (hypothalamus), A5 (midbrain), A6 (pons), A7 (medulla), A8 (cerebellum), and A9 (olfactory bulb). (E) Correlation of the amount of donepezil from different cerebrum regions determined by MALDI-MSI and LC – MS/MS. Adapted with permission from [92]. Copyright 2022 ACS.