{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T19:45:06Z","timestamp":1787946306516,"version":"build-2784847793"},"reference-count":70,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,6,11]],"date-time":"2025-06-11T00:00:00Z","timestamp":1749600000000},"content-version":"vor","delay-in-days":10,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Separation Science"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>The aim of this work was to develop the HPLC\u2010MS\/MS method for the determination of L\u2010carnitine and creatine in tears, as these molecules can be used as biomarkers of several diseases and health conditions with neurological manifestation, simultaneously with the determination of creatinine as normalization factor.<\/jats:p>\n                  <jats:p>\n                    Tears were collected using a microtube during crying or using Schirmer strip by inserting it under the lower eyelid. Due to the low stability of creatine, only a few hours at room temperature, it is advisable to freeze the samples immediately after collection. Different methanol to water contents in the extraction solution were tested (0%\u2013100%). Extraction recovery from Schirmer strips, matrix effect, and overall process efficiency were evaluated for 0.3 and 1\u00a0mL of extraction solution used. Finally, the extraction into 1\u00a0mL of 80% methanol containing 0.1% formic acid, and subsequent HPLC\u2010MS\/MS separation at isocratic conditions (methanol:water 5:95% with 0.1% formic acid and flow rate of 0.25\u00a0mL\/min) using a Synergi 4 \u03bc Polar\u2010RP column (150 \u00d7 2\u00a0mm) and detection in the positive ion mode was used. The limits of quantifications for L\u2010carnitine, creatine, and creatinine in tears were 0.5, 1.0, and 1.0 \u00b5mol\/L, respectively. Intraday and interday precisions were up to 4.4% and bias did not exceed 12% for all analytes. Linearity was tested and approved in the range of 0.23\u201330 \u00b5mol\/L for L\u2010carnitine and 0.78\u2013100 \u00b5mol\/L for creatine and creatinine. Measured values of L\u2010carnitine, creatine, and creatinine in real tear samples of healthy individuals (\n                    <jats:italic>n<\/jats:italic>\n                    = 7) were within the range of 1.1\u20138.2, 4.8\u201346.3, and 8\u201344.7 \u00b5mol\/L, respectively. Obtained results were compared with published results in tears if available (L\u2010carnitine and creatinine) or with other biological matrices. As our knowledge, this publication is the first that reports the content of creatine in tears.\n                  <\/jats:p>","DOI":"10.1002\/jssc.70193","type":"journal-article","created":{"date-parts":[[2025,6,12]],"date-time":"2025-06-12T01:06:19Z","timestamp":1749690379000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Development of the High\u2010Performance Liquid Chromatography\u2010Tandem Mass Spectrometry Method for the Determination of Creatine, L\u2010Carnitine, and Creatinine in Tears"],"prefix":"10.1002","volume":"48","author":[{"given":"Helena","family":"Jurd\u00e1kov\u00e1","sequence":"first","affiliation":[{"name":"Faculty of Natural Sciences, Department of Analytical Chemistry Comenius University in Bratislava  Bratislava Slovak Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michaela","family":"\u0160imurdov\u00e1","sequence":"additional","affiliation":[{"name":"Faculty of Natural Sciences, Department of Analytical Chemistry Comenius University in Bratislava  Bratislava Slovak Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ren\u00e1ta","family":"G\u00f3rov\u00e1","sequence":"additional","affiliation":[{"name":"Faculty of Natural Sciences, Department of Analytical Chemistry Comenius University in Bratislava  Bratislava Slovak Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,6,11]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41433\u2010020\u20100930\u20100"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.3109\/02713688609029235"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014\u20104835(84)90012\u20105"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/0002\u20109394(68)93093\u20106"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1136\/bjo.34.12.737"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00496763"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ab.2021.114295"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00164671"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10517\u2010023\u201005893\u20100"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2018.11.015"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms232314864"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ab.2023.115448"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/jdi.13344"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010019\u201041066\u20108"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/sscp.202200098"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13167\u2010016\u20100065\u20103"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13167\u2010021\u201000265\u2010y"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13167\u2010022\u201000272\u20107"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0158000"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010019\u201051837\u2010y"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms231710123"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.2217\/bmm\u20102019\u20100364"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.parkreldis.2019.03.001"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20061265"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.3390\/s23115251"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1097\/ICL.0000000000000663"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsmeasuresciau.3c00067"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.survophthal.2022.01.010"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.10\u20105687"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.3892\/ijmm.2021.4916"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jprot.2012.04.053"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajo.2010.11.003"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1021\/pr2004874"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.4331\/wjbc.v10.i1.7"},{"key":"e_1_2_11_36_1","first-page":"39","article-title":"What Is the Evidence of Mitochondrial Dysfunction in Autism Spectrum Disorders?","volume":"59","author":"Babinsk\u00e1 K.","year":"2017","journal-title":"Activitas Nervosa Superior Rediviva"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm10061202"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.AW119.008137"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/bies.201700012"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2009.07.015"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2019\u20103460"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet\u20102013\u2010101658"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10803\u2010022\u201005860\u20100"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1097\/DBP.0000000000000299"},{"key":"e_1_2_11_45_1","first-page":"43","article-title":"Creatine Deficiency Syndromes, Biomarkers and Potential Frequency in Children With Autism Spectrum Disorders","volume":"6","author":"Jurd\u00e1kov\u00e1 H.","year":"2018","journal-title":"Zdravotn\u00edcke Listy"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1002\/jssc.200500428"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arabjc.2024.105818"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinbiochem.2010.08.004"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinbiochem.2008.10.001"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1005383507547"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpba.2011.06.006"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.aca.2018.03.038"},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.1007\/978\u20101\u20100716\u20102565\u20101_12"},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2014.01.019"},{"key":"e_1_2_11_55_1","doi-asserted-by":"publisher","DOI":"10.1002\/jssc.200900659"},{"key":"e_1_2_11_56_1","doi-asserted-by":"publisher","DOI":"10.1002\/jssc.200900171"},{"key":"e_1_2_11_57_1","doi-asserted-by":"publisher","DOI":"10.1002\/jssc.200900270"},{"key":"e_1_2_11_58_1","doi-asserted-by":"publisher","DOI":"10.1002\/jssc.200900727"},{"key":"e_1_2_11_59_1","doi-asserted-by":"publisher","DOI":"10.1097\/OPX.0b013e318194e767"},{"key":"e_1_2_11_60_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0073076"},{"key":"e_1_2_11_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jemermed.2017.11.022"},{"key":"e_1_2_11_62_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.analchem.9b05078"},{"key":"e_1_2_11_63_1","volume-title":"ICH Guideline M10 on Bioanalytical Method Validation and Study Sample Analysis Step5","author":"European Medicines Agency, Committee for Medicinal Products for Human Use","year":"2022"},{"key":"e_1_2_11_64_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11306\u2010016\u20101137\u2010z"},{"key":"e_1_2_11_65_1","doi-asserted-by":"publisher","DOI":"10.1111\/ped.15072"},{"key":"e_1_2_11_66_1","first-page":"71","article-title":"Diagnostic of Cerebral Creatine Deficiency Syndromes Using Tandem Mass Spectrometry in Urine and Dry Urine Spot","volume":"11","author":"Jurd\u00e1kov\u00e1 H.","year":"2023","journal-title":"Zdravotn\u00edcke Listy"},{"key":"e_1_2_11_67_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11306\u2010006\u20100042\u20102"},{"key":"e_1_2_11_68_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00769\u2010002\u20100487\u20106"},{"key":"e_1_2_11_69_1","doi-asserted-by":"publisher","DOI":"10.4155\/bio\u20102017\u20100214"},{"key":"e_1_2_11_70_1","doi-asserted-by":"publisher","DOI":"10.1039\/D3GC02347H"},{"key":"e_1_2_11_71_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022\u2010510X(97)00314\u20106"}],"container-title":["Journal of Separation Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jssc.70193","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T08:42:39Z","timestamp":1764664959000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/jssc.70193"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6]]},"references-count":70,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2025,6]]}},"alternative-id":["10.1002\/jssc.70193"],"URL":"https:\/\/doi.org\/10.1002\/jssc.70193","archive":["Portico"],"relation":{},"ISSN":["1615-9306","1615-9314"],"issn-type":[{"value":"1615-9306","type":"print"},{"value":"1615-9314","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6]]},"assertion":[{"value":"2025-02-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-05-27","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-06-11","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70193"}}