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In this study, we applied three different tools of MSI, desorption electrospray ionization (DESI)-MSI, matrix-assisted laser desorption ionization (MALDI)-MSI, and a newly developed atmospheric pressure (AP)-MALDI-MSI known as iMScopeTM QT for rapid mapping of imipramine, chloroquine, and their metabolites in C57BL\/6 male wild-type mice. Among three MSI tools, better detection capability for targeted drugs at higher speed (up to 32 pixels\/s) was observed in iMScope QT. It revealed that imipramine and its metabolites were significantly accumulated in the renal cortex of mice, but chloroquine and its metabolites were highly accumulated in the renal pelvis and renal medulla of mice. Additionally, a higher accumulation of imipramine was noted in the thalamus, hypothalamus, septum, and hindbrain of mice brains. However, chloroquine and its metabolites showed notable accumulation in the lateral ventricle, fourth ventricle, and fornix of the mice brains. These findings of our study can be helpful in understanding clinically relevant properties, efficacy, and potential side effects of these drugs. Our study also showed the potentiality of iMScope QT for rapid mapping of small drugs and their metabolites in biological samples.<\/jats:p>","DOI":"10.3390\/ph15111314","type":"journal-article","created":{"date-parts":[[2022,10,26]],"date-time":"2022-10-26T05:11:33Z","timestamp":1666761093000},"page":"1314","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Application of AP-MALDI Imaging Mass Microscope for the Rapid Mapping of Imipramine, Chloroquine, and Their Metabolites in the Kidney and Brain of Wild-Type Mice"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7497-3540","authenticated-orcid":false,"given":"Ariful","family":"Islam","sequence":"first","affiliation":[{"name":"Department of Cellular & Molecular Anatomy, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka 431-3192, Japan"},{"name":"Preppers Co., Ltd., Hamamatsu University School of Medicine, Hamamatsu, Shizuoka 431-3192, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takumi","family":"Sakamoto","sequence":"additional","affiliation":[{"name":"Department of Cellular & Molecular Anatomy, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka 431-3192, Japan"},{"name":"Preppers Co., Ltd., Hamamatsu University School of Medicine, Hamamatsu, Shizuoka 431-3192, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Zhai","sequence":"additional","affiliation":[{"name":"Department of Cellular & Molecular Anatomy, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka 431-3192, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Md. 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Al","family":"Mamun","sequence":"additional","affiliation":[{"name":"Department of Cellular & Molecular Anatomy, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka 431-3192, Japan"},{"name":"Preppers Co., Ltd., Hamamatsu University School of Medicine, Hamamatsu, Shizuoka 431-3192, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yutaka","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Department of Cellular & Molecular Anatomy, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka 431-3192, Japan"},{"name":"Preppers Co., Ltd., Hamamatsu University School of Medicine, Hamamatsu, Shizuoka 431-3192, Japan"},{"name":"International Mass Imaging Center, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka 431-3192, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoaki","family":"Kahyo","sequence":"additional","affiliation":[{"name":"Department of Cellular & Molecular Anatomy, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka 431-3192, Japan"},{"name":"Preppers Co., Ltd., Hamamatsu University School of Medicine, Hamamatsu, Shizuoka 431-3192, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitsutoshi","family":"Setou","sequence":"additional","affiliation":[{"name":"Department of Cellular & Molecular Anatomy, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka 431-3192, Japan"},{"name":"International Mass Imaging Center, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka 431-3192, Japan"},{"name":"Department of Systems Molecular Anatomy, Institute for Medical Photonics Research, Preeminent Medical Photonics Education & Research Center, Hamamatsu, Shizuoka 431-3192, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1021\/acs.analchem.7b04733","article-title":"Mass spectrometry imaging: A review of emerging advancements and future insights","volume":"90","author":"Buchberger","year":"2018","journal-title":"Anal. Chem."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"5533","DOI":"10.1038\/s41596-021-00624-z","article-title":"Label-free cell assays to determine compound uptake or drug action using MALDI-TOF mass spectrometry","volume":"16","author":"Unger","year":"2021","journal-title":"Nat. Protoc."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"116482","DOI":"10.1016\/j.trac.2021.116482","article-title":"Mass spectrometry imaging in drug distribution and drug metabolism studies\u2013Principles, applications and perspectives","volume":"146","author":"Granborg","year":"2022","journal-title":"TrAC Trends Anal. Chem."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1566","DOI":"10.1126\/science.1119426","article-title":"Ambient mass spectrometry","volume":"311","author":"Cooks","year":"2006","journal-title":"Science"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Mamun, M.A., Sato, S., Naru, E., Sakata, O., Hoshikawa, E., Suzuki, A., Islam, A., Kahyo, T., Sato, T., and Ito, T.K. (2020). Higher Accumulation of Docosahexaenoic Acid in the Vermilion of the Human Lip than in the Skin. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21082807"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Takeyama, E., Islam, A., Watanabe, N., Tsubaki, H., Fukushima, M., Mamun, M.A., Sato, S., Sato, T., Eto, F., and Yao, I. (2019). Dietary intake of green nut oil or DHA ameliorates DHA distribution in the brain of a mouse model of dementia accompanied by memory recovery. Nutrients, 11.","DOI":"10.3390\/nu11102371"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Xie, F., Groseclose, M.R., Tortorella, S., Cruciani, G., and Castellino, S. (2022). Mapping the Lipids of Skin Sebaceous Glands and Hair Follicles by High Spatial Resolution MALDI Imaging Mass Spectrometry. Pharmaceuticals, 15.","DOI":"10.3390\/ph15040411"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"4751","DOI":"10.1021\/ac970888i","article-title":"Molecular imaging of biological samples: Localization of peptides and proteins using MALDI-TOF MS","volume":"69","author":"Caprioli","year":"1997","journal-title":"Anal. Chem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"9316","DOI":"10.1021\/acs.analchem.2c00754","article-title":"FT-ICR Mass Spectrometry Imaging at Extreme Mass Resolving Power Using a Dynamically Harmonized ICR Cell with 1\u03c9 or 2\u03c9 Detection","volume":"94","author":"Tiquet","year":"2022","journal-title":"Anal. Chem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1021\/ac990998k","article-title":"Atmospheric pressure matrix-assisted laser desorption\/ionization mass spectrometry","volume":"72","author":"Laiko","year":"2000","journal-title":"Anal. Chem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"9153","DOI":"10.1021\/ac901872n","article-title":"Visualization of volatile substances in different organelles with an atmospheric-pressure mass microscope","volume":"81","author":"Harada","year":"2009","journal-title":"Anal. Chem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1463","DOI":"10.1007\/s13361-018-1928-8","article-title":"AP-MALDI mass spectrometry imaging of gangliosides using 2, 6-dihydroxyacetophenone","volume":"29","author":"Jackson","year":"2018","journal-title":"J. Am. Soc. Mass Spectrom."},{"key":"ref_13","unstructured":"Fayez, R., and Gupta, V. (2022, October 19). Imipramine, Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK557656\/."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/j.jcrc.2020.03.005","article-title":"A systematic review on the efficacy and safety of chloroquine for the treatment of COVID-19","volume":"57","author":"Cortegiani","year":"2020","journal-title":"J. Crit. Care"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1080\/15563650.2020.1817479","article-title":"Toxicity of chloroquine and hydroxychloroquine following therapeutic use or overdose","volume":"59","author":"Doyno","year":"2021","journal-title":"Clin. Toxicol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1687","DOI":"10.3389\/fphar.2019.01687","article-title":"Imipramine and venlafaxine differentially affect primary glial cultures of prenatally stressed rats","volume":"10","author":"Obuchowicz","year":"2020","journal-title":"Front. Pharmacol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1093\/chromsci\/bmv187","article-title":"A simple, rapid and reliable method to determine imipramine and desipramine in mouse serum using ultra-high-performance liquid chromatography\u2013quadrupole-time-of-flight mass spectrometry","volume":"54","author":"Zhao","year":"2016","journal-title":"J. Chromatogr. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1016\/j.jpba.2009.01.013","article-title":"Identification and characterization of process related impurities in chloroquine and hydroxychloroquine by LC\/IT\/MS, LC\/TOF\/MS and NMR","volume":"49","author":"Dongre","year":"2009","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"333","DOI":"10.4155\/bio-2018-0202","article-title":"High sensitivity methods to quantify chloroquine and its metabolite in human blood samples using LC\u2013MS\/MS","volume":"11","author":"Kaewkhao","year":"2019","journal-title":"Bioanalysis"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Fresnais, M., Liang, S., Breitkopf, M., Lindner, J.R., Claude, E., Pringle, S., Levkin, P.A., Demir, K., Benzel, J., and Sundheimer, J. (2022). Analytical Performance Evaluation of New DESI Enhancements for Targeted Drug Quantification in Tissue Sections. Pharmaceuticals, 15.","DOI":"10.3390\/ph15060694"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1016\/j.jfda.2019.05.004","article-title":"Analysis of potential anti-aging beverage Pru, a traditional Cuban refreshment, by desorption electrospray ionization-mass spectrometry and FTICR tandem mass spectrometry","volume":"27","author":"Gonzalez","year":"2019","journal-title":"J. Food Drug Anal."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"106881","DOI":"10.1016\/j.clineuro.2021.106881","article-title":"The stability of the metabolic turnover of arachidonic acid in human unruptured intracranial aneurysmal walls is sustained","volume":"208","author":"Takeda","year":"2021","journal-title":"Clin. Neurol. Neurosurg."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1600","DOI":"10.1002\/rcm.5021","article-title":"Distribution of chloroquine in ocular tissue of pigmented rat using matrix-assisted laser desorption\/ionization imaging quadrupole time-of-flight tandem mass spectrometry","volume":"25","author":"Yamada","year":"2011","journal-title":"Rapid Commun. Mass Spectrom."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Mori, N., Mochizuki, T., Yamazaki, F., Takei, S., Mano, H., Matsugi, T., and Setou, M. (2019). MALDI imaging mass spectrometry revealed atropine distribution in the ocular tissues and its transit from anterior to posterior regions in the whole-eye of rabbit after topical administration. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0211376"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2164","DOI":"10.1021\/ac2025317","article-title":"MALDI imaging and structural analysis of rat brain lipid negative ions with 9-aminoacridine matrix","volume":"84","author":"Cerruti","year":"2012","journal-title":"Anal. Chem."},{"key":"ref_26","first-page":"457","article-title":"Drug-induced impairment of renal function","volume":"7","author":"Pazhayattil","year":"2014","journal-title":"Int. J. Nephrol. Renov. Dis."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2291","DOI":"10.3390\/ph3072291","article-title":"Nonsteroidal anti-inflammatory drugs and the kidney","volume":"3","year":"2010","journal-title":"Pharmaceuticals"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Chang, G.-R., Hou, P.-H., Wang, C.-M., Lin, J.-W., Lin, W.-L., Lin, T.-C., Liao, H.-J., Chan, C.-H., and Wang, Y.-C. (2021). Imipramine Accelerates Nonalcoholic Fatty Liver Disease, Renal Impairment, Diabetic Retinopathy, Insulin Resistance, and Urinary Chromium Loss in Obese Mice. Vet. Sci., 8.","DOI":"10.3390\/vetsci8090189"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1081\/JDI-200031761","article-title":"Attenuation of Chloroquine-Induced Renal Damage by \u03b1-Lipoic Acid: Possible Antioxidant Mechanism","volume":"26","author":"Murugavel","year":"2004","journal-title":"Ren. Fail."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1080\/0886022X.2022.2046609","article-title":"Hydroxychloroquine\/chloroquine and the risk of acute kidney injury in COVID-19 patients: A systematic review and meta-analysis","volume":"44","author":"Liao","year":"2022","journal-title":"Ren. Fail."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/j.bbi.2016.05.008","article-title":"Antidepressant imipramine diminishes stress-induced inflammation in the periphery and central nervous system and related anxiety-and depressive-like behaviors","volume":"57","author":"Ramirez","year":"2016","journal-title":"Brain Behav. Immun."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"fcac100","DOI":"10.1093\/braincomms\/fcac100","article-title":"Serotonin\u2013norepinephrine reuptake inhibitor antidepressant effects on regional connectivity of the thalamus in persistent depressive disorder: Evidence from two randomized, double-blind, placebo-controlled clinical trials","volume":"4","author":"Yang","year":"2022","journal-title":"Brain Commun."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/2045-8118-11-10","article-title":"A new look at cerebrospinal fluid circulation","volume":"11","author":"Brinker","year":"2014","journal-title":"Fluids Barriers CNS"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"737217","DOI":"10.3389\/fnhum.2021.737217","article-title":"A Brief Overview of the Cerebrospinal Fluid System and Its Implications for Brain and Spinal Cord Diseases","volume":"15","author":"Wichmann","year":"2021","journal-title":"Front. Hum. Neurosci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"416","DOI":"10.2176\/nmc.ra.2016-0020","article-title":"Research into the physiology of cerebrospinal fluid reaches a new horizon: Intimate exchange between cerebrospinal fluid and interstitial fluid may contribute to maintenance of homeostasis in the central nervous system","volume":"56","author":"Matsumae","year":"2016","journal-title":"Neurol. Med.-Chir."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1136\/jnnp-2019-322375","article-title":"Anatomy and function of the fornix in the context of its potential as a therapeutic target","volume":"91","author":"Senova","year":"2020","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1710","DOI":"10.1086\/430180","article-title":"Neurotoxicity due to antimalarial therapy associated with misdiagnosis of malaria","volume":"40","author":"Dismukes","year":"2005","journal-title":"Clin. Infect. Dis."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Islam, A., Takeyama, E., Mamun, M., Sato, T., Horikawa, M., Takahashi, Y., Kikushima, K., and Setou, M. (2020). Green nut oil or DHA supplementation restored decreased distribution levels of DHA containing phosphatidylcholines in the brain of a mouse model of dementia. Metabolites, 10.","DOI":"10.3390\/metabo10040153"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.bbrc.2022.04.004","article-title":"Stress upregulates 2-arachidonoylglycerol levels in the hypothalamus, midbrain, and hindbrain, and it is sustained by green nut oil supplementation in SAMP8 mice revealed by DESI-MSI","volume":"609","author":"Islam","year":"2022","journal-title":"Biochem. Biophys. Res. Commun."}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/15\/11\/1314\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:02:33Z","timestamp":1760144553000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/15\/11\/1314"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,25]]},"references-count":39,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2022,11]]}},"alternative-id":["ph15111314"],"URL":"https:\/\/doi.org\/10.3390\/ph15111314","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,25]]}}}