{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T16:42:35Z","timestamp":1776271355038,"version":"3.50.1"},"reference-count":30,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2022,6,25]],"date-time":"2022-06-25T00:00:00Z","timestamp":1656115200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Tier 1 grant from the Ministry of Education, Singapore","award":["R-148-000-104-112"],"award-info":[{"award-number":["R-148-000-104-112"]}]},{"name":"Tier 1 grant from the Ministry of Education, Singapore","award":["20221026"],"award-info":[{"award-number":["20221026"]}]},{"name":"Pedagogical Research and Reform Grant from the Shenzhen Technology University","award":["R-148-000-104-112"],"award-info":[{"award-number":["R-148-000-104-112"]}]},{"name":"Pedagogical Research and Reform Grant from the Shenzhen Technology University","award":["20221026"],"award-info":[{"award-number":["20221026"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The immediate and delayed metabolic changes in rats treated with valproate (VPA), a drug used for the treatment of epilepsy, were profiled. An established approach using dried blood spots (DBS) as sample matrices for gas chromatography\/mass spectrometry-based metabolomics profiling was modified using double solvents in the extraction of analytes. With the modified method, some of the previously undetectable metabolites were recovered and subtle differences in the metabolic changes upon exposure to a single dose of VPA between males and female rats were identified. In male rats, changes in 2-hydroxybutyric acid, pipecolic acid, tetratriacontane and stearic acid were found between the control and treatment groups at various time points from 2.5 h up to 24 h. In contrast, such differences were not observed in female rats, which could be caused by the vast inter-individual variations in metabolite levels within the female group. Based on the measured DBS drug concentrations, clearance and apparent volume of distribution of VPA were estimated and the values were found to be comparable to those estimated previously from full blood drug concentrations. The current study indicated that DBS is a powerful tool to monitor drug levels and metabolic changes in response to drug treatment.<\/jats:p>","DOI":"10.3390\/ijms23137083","type":"journal-article","created":{"date-parts":[[2022,6,26]],"date-time":"2022-06-26T09:00:13Z","timestamp":1656234013000},"page":"7083","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Dried Blood Spots as Matrix for Evaluation of Valproate Levels and the Immediate and Delayed Metabolomic Changes Induced by Single Valproate Dose Treatment"],"prefix":"10.3390","volume":"23","author":[{"given":"Sing Teang","family":"Kong","sequence":"first","affiliation":[{"name":"Department of Pharmacy, National University of Singapore, 18 Science Drive 4, Singapore 117543, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6034-1363","authenticated-orcid":false,"given":"Hai-Shu","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, National University of Singapore, 18 Science Drive 4, Singapore 117543, Singapore"},{"name":"College of Pharmacy, Shenzhen Technology University, Shenzhen 518118, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianhong","family":"Ching","sequence":"additional","affiliation":[{"name":"Duke-NUS Medical School, 8 College Road, Singapore 169857, Singapore"},{"name":"KK Research Centre, KK Women\u2019s and Children\u2019s Hospital, Singapore 229899, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huiqing","family":"Xie","sequence":"additional","affiliation":[{"name":"Institute of Materials Research and Engineering, Agency for Science Technology and Research, Singapore 138634, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul C.","family":"Ho","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, National University of Singapore, 18 Science Drive 4, Singapore 117543, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Gonzalez-Covarrubias, V., Martinez-Martinez, E., and Del Bosque-Plata, L. 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