{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T05:49:43Z","timestamp":1784958583743,"version":"3.55.0"},"reference-count":28,"publisher":"Wiley","issue":"23","license":[{"start":{"date-parts":[[2021,10,20]],"date-time":"2021-10-20T00:00:00Z","timestamp":1634688000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100007594","name":"Univerzita Komensk\u00e9ho v Bratislave","doi-asserted-by":"publisher","award":["UK\/88\/2021"],"award-info":[{"award-number":["UK\/88\/2021"]}],"id":[{"id":"10.13039\/100007594","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003193","name":"Ministerstvo \u0161kolstva, vedy, v\u00fdskumu a \u0161portu Slovenskej republiky","doi-asserted-by":"publisher","award":["VEGA 1\/0081\/20"],"award-info":[{"award-number":["VEGA 1\/0081\/20"]}],"id":[{"id":"10.13039\/501100003193","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003193","name":"Ministerstvo \u0161kolstva, vedy, v\u00fdskumu a \u0161portu Slovenskej republiky","doi-asserted-by":"publisher","award":["VEGA 1\/0255\/18"],"award-info":[{"award-number":["VEGA 1\/0255\/18"]}],"id":[{"id":"10.13039\/501100003193","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003194","name":"Agent\u00fara Ministerstva \u0161kolstva, vedy, v\u00fdskumu a \u0161portu SR","doi-asserted-by":"publisher","award":["APVV\u201018\u20100084"],"award-info":[{"award-number":["APVV\u201018\u20100084"]}],"id":[{"id":"10.13039\/501100003194","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Separation Science"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Caffeine is a widely consumed psychostimulant with several mechanisms of action and various positive and negative effects on organisms. Caffeine undergoes extensive hepatic metabolism to form main metabolites such as theobromine, theophylline, paraxanthine, and 1,3,7\u2010trimethyluric acid. However, interspecies diversities have been observed in caffeine metabolism. In the present study, we developed a sensitive and straightforward ultra\u2010high\u2010performance liquid chromatography\u2010tandem mass spectrometry method to quantify caffeine and its primary metabolites, namely theobromine, theophylline, paraxanthine, and 1,3,7\u2010trimethyluric acid in rat plasma. After extraction of analytes using micro solid\u2010phase extraction plate, analytes were separated by elution gradient on the Acquity UPLC HSS T3 (50 \u00d7 2.1\u00a0mm, 1.8 \u03bcm) column over 4\u00a0min. The detection was done on a triple quadrupole tandem mass spectrometer by multiple reaction monitoring modes using a positive electrospray ionization interface. The method was successfully validated according to the European Medicine Agency guideline over a concentration range of 5\u20131500\u00a0ng\/ml for caffeine, 5\u20131200\u00a0ng\/mL for theobromine, and 2.5\u20131200\u00a0ng\/mL for theophylline, paraxanthine, and 1,3,7\u2010trimethyluric acid. The developed method was applied to analyze samples from animal experiments focusing on the metabolism and effects of caffeine and caffeine\u2010containing beverages.<\/jats:p>","DOI":"10.1002\/jssc.202100604","type":"journal-article","created":{"date-parts":[[2021,10,9]],"date-time":"2021-10-09T08:01:40Z","timestamp":1633766500000},"page":"4274-4283","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Simultaneous determination of caffeine and its metabolites in rat plasma by UHPLC\u2010MS\/MS"],"prefix":"10.1002","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1095-6810","authenticated-orcid":false,"given":"Martin","family":"Kertys","sequence":"first","affiliation":[{"name":"Department of Pharmacology Jessenius Faculty of Medicine in Martin Comenius University  Bratislava Slovakia"},{"name":"Biomedical Center Martin Jessenius Faculty of Medicine in Martin Comenius University  Bratislava Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nela","family":"\u017didekov\u00e1","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Jessenius Faculty of Medicine in Martin Comenius University  Bratislava Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristi\u00e1n","family":"Pr\u0161o","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Jessenius Faculty of Medicine in Martin Comenius University  Bratislava Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2170-6582","authenticated-orcid":false,"given":"Katar\u00edna","family":"Mar\u00e1kov\u00e1","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Analysis and Nuclear Pharmacy Faculty of Pharmacy Comenius University  Bratislava Slovakia"},{"name":"Toxicological and Antidoping Center Faculty of Pharmacy Comenius University  Bratislava Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katar\u00edna","family":"Kme\u0165ov\u00e1","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biomedicine Faculty of Medicine Comenius University  Bratislava Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juraj","family":"Mokr\u00fd","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Jessenius Faculty of Medicine in Martin Comenius University  Bratislava Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,10,20]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1816604"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.117.014407"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nutres.2020.05.005"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-642-13443-2_3"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-2010-1379"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.2174\/1570159X13666141210215655"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-007-7051-9"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.foodres.2014.03.009"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.physbeh.2011.07.027"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1515\/acm-2017-0012"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0955-2863(02)00216-4"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2006.12.004"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fct.2013.08.073"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejcn.2012.11"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.foodchem.2013.05.069"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/bmc.5141"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchromb.2009.12.019"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/bmc.3900"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vascn.2020.106946"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.4155\/bio.14.149"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpba.2011.12.033"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12272-011-0114-3"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chroma.2014.05.047"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/JSSC.202100443"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/jssc.200800655"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/jssc.200401841"},{"key":"e_1_2_9_28_1","unstructured":"European Medicines Agency (EMA) Committee for Medicinal Products for Human Use (CHMP).Guideline on bioanalytical method validation. EMEA\/CHMP\/EWP\/192217\/2009 Rev. 1 Corr. 2**. 21 July 2011 Eff. 1 Febr. 2012; 2012 44 1\u201323."},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1080\/10408347.2014.980775"}],"container-title":["Journal of Separation Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jssc.202100604","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jssc.202100604","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jssc.202100604","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,19]],"date-time":"2025-10-19T08:40:19Z","timestamp":1760863219000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/jssc.202100604"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,20]]},"references-count":28,"journal-issue":{"issue":"23","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["10.1002\/jssc.202100604"],"URL":"https:\/\/doi.org\/10.1002\/jssc.202100604","archive":["Portico"],"relation":{},"ISSN":["1615-9306","1615-9314"],"issn-type":[{"value":"1615-9306","type":"print"},{"value":"1615-9314","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,20]]},"assertion":[{"value":"2021-08-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-10-01","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-10-20","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}