{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T06:24:50Z","timestamp":1767853490646,"version":"3.49.0"},"reference-count":29,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2013,12,5]],"date-time":"2013-12-05T00:00:00Z","timestamp":1386201600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Rapid Comm Mass Spectrometry"],"published-print":{"date-parts":[[2014,1,30]]},"abstract":"<jats:sec>\n                    <jats:title>RATIONALE<\/jats:title>\n                    <jats:p>Although Desorption Electrospray Ionization (DESI) Mass Spectrometry Imaging (MSI) is uniquely suited for whole\u2010body (WB) tissue distribution study of drugs, success in this area has been difficult. Here, we present WB tissue distribution studies using DESI\u2010MSI and a new histological tissue\u2010friendly solvent system.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      Neonate pups were dosed subcutaneously (SC) with clozapine, compound\n                      <jats:bold>1<\/jats:bold>\n                      , compound\n                      <jats:bold>2<\/jats:bold>\n                      , or compound\n                      <jats:bold>3<\/jats:bold>\n                      . Following euthanization by hypothermia, neonates underwent a transcardiac perfusion (saline) to remove blood. After cryosectioning, DESI\u2010MSI was conducted for the WB tissue slides, followed sequentially by histological staining.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      Whole\u2010body tissue imaging showed that clozapine and its\n                      <jats:italic>N<\/jats:italic>\n                      \u2010oxide metabolite were distributed in significant amounts in the brain, spinal cord, liver, heart (ventricle), and lungs. Compound\n                      <jats:bold>1<\/jats:bold>\n                      was distributed mainly in the liver and muscle, and its mono\u2010oxygenated metabolite was detected by DESI\u2010MSI exclusively in the liver. Compound\n                      <jats:bold>2<\/jats:bold>\n                      was distributed mainly in the muscle and fatty tissue. Compound\n                      <jats:bold>3<\/jats:bold>\n                      was distributed mainly in fatty tissue and its metabolites were also mainly detected in the same tissue.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS<\/jats:title>\n                    <jats:p>The results demonstrate the successful application of DESI\u2010MSI in whole\u2010body tissue distribution studies of drugs and metabolites in combination with sequential histology staining for anatomy. The results also identified lipophilicity as the driving force in the tissue distribution of the three Amgen compounds. Copyright \u00a9 2013 John Wiley &amp; Sons, Ltd.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/rcm.6775","type":"journal-article","created":{"date-parts":[[2013,12,15]],"date-time":"2013-12-15T20:04:02Z","timestamp":1387137842000},"page":"185-190","source":"Crossref","is-referenced-by-count":29,"title":["Whole\u2010body tissue distribution study of drugs in neonate mice using desorption electrospray ionization mass spectrometry imaging"],"prefix":"10.1002","volume":"28","author":[{"given":"Jingzhou","family":"Liu","sequence":"first","affiliation":[{"name":"Pharmacokinetics and Drug Metabolism Amgen Inc.  360 Binney Street Cambridge MA 02142 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacinthe","family":"Gingras","sequence":"additional","affiliation":[{"name":"Neuroscience Amgen Inc.  360 Binney Street Cambridge MA 02142 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenneth P.","family":"Ganley","sequence":"additional","affiliation":[{"name":"Comparative Biology and Safety Sciences Amgen Inc.  360 Binney Street Cambridge MA 02142 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ramin","family":"Vismeh","sequence":"additional","affiliation":[{"name":"Pharmacokinetics and Drug Metabolism Amgen Inc.  360 Binney Street Cambridge MA 02142 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yohannes","family":"Teffera","sequence":"additional","affiliation":[{"name":"Pharmacokinetics and Drug Metabolism Amgen Inc.  360 Binney Street Cambridge MA 02142 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhiyang","family":"Zhao","sequence":"additional","affiliation":[{"name":"Pharmacokinetics and Drug Metabolism Amgen Inc.  360 Binney Street Cambridge MA 02142 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2013,12,5]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/jms.1876"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.4155\/bio.11.282"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/mas.20124"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth1094"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1021\/ac970888i"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/pmic.200701025"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.200602449"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1021\/ac801662n"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1021\/ac102264z"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbalip.2011.03.004"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1021\/ac902245p"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/jms.525"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1021\/ac060788p"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0801066105"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1021\/ac800546a"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jprot.2011.03.019"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.5650\/jos.58.415"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1021\/ac201949b"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1359-6446(05)03458-6"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1039\/c1an00008j"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijms.2006.08.003"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mad.2004.09.032"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-60761-746-4_17"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1021\/ac8015467"},{"key":"e_1_2_6_26_1","doi-asserted-by":"crossref","DOI":"10.17226\/25801","volume-title":"Guide for the Care and Use of Laboratory Animals","author":"National Research Council (US) Committee for the Update of the Guide for the Care and Use of Laboratory Animals","year":"2011"},{"key":"e_1_2_6_27_1","first-page":"96","volume-title":"Histotechnology: A Self\u2010instructional Text","author":"Carson F. 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