{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T12:00:39Z","timestamp":1783771239069,"version":"3.55.0"},"reference-count":32,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2023,12,1]],"date-time":"2023-12-01T00:00:00Z","timestamp":1701388800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Biomedical Chromatography"],"published-print":{"date-parts":[[2024,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>A method using ultrahigh\u2010performance liquid chromatography\u2013tandem mass spectrometry was developed, validated, and applied to simultaneously determine plasma methotrexate (MTX) and 7\u2010hydroxy\u2010methotrexate (7\u2010OH\u2010MTX) in 117 patients with central nervous system (CNS) lymphoma. The ion transitions utilized were <jats:italic>m\/z<\/jats:italic> 455.2 &gt; 308.2 for MTX and <jats:italic>m\/z<\/jats:italic> 471.2 &gt; 324.1 for 7\u2010OH\u2010MTX. Samples were prepared through protein precipitation using methanol. Chromatographic separation was achieved within 3.0 min on a CMS9030 column (Ruixi, 2.1 \u00d7 50 mm, 3 \u03bcm) through a gradient elution of methanol and a 10% ammonium acetate solution at a flow rate of 0.4 mL\/min. The method demonstrated linearity in the concentration range of 0.05\u201310 \u03bcM for MTX and 0.25\u201350 \u03bcM for 7\u2010OH\u2010MTX. The intra\u2010 and inter\u2010day inaccuracy ranged from \u20137.38% to 7.83%, and the imprecision was less than 6.00% for both analytes. The recovery and matrix effect normalized by the internal standard (MTX\u2010D<jats:sub>3<\/jats:sub>) remained consistent. Both analytes remained stable under nine different storage conditions. In patients with CNS lymphoma, MTX levels at 12 h and 7\u2010OH\u2010MTX levels at 12, 36, and 60 h after dosing in individuals with impaired renal function were significantly higher compared with those with normal renal function. 7\u2010OH\u2010MTX could potentially serve as a superior indicator for nephrotoxicity compared with MTX.<\/jats:p>","DOI":"10.1002\/bmc.5789","type":"journal-article","created":{"date-parts":[[2023,12,1]],"date-time":"2023-12-01T03:26:42Z","timestamp":1701401202000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["An ultrahigh\u2010performance liquid chromatography\u2013tandem mass spectrometry method for quantification of methotrexate and 7\u2010hydroxy\u2010methotrexate and application for therapeutic drug monitoring in patients with central nervous system lymphoma"],"prefix":"10.1002","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6611-966X","authenticated-orcid":false,"given":"Jiping","family":"Huo","sequence":"first","affiliation":[{"name":"Department of Pharmacy, Beijing Tiantan Hospital Capital Medical University  Beijing P. R. China"},{"name":"Department of Clinical Pharmacology, College of Pharmaceutical Sciences Capital Medical University  Beijing Beijing P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Beijing Health Vocational College  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongjie","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Beijing Tiantan Hospital Capital Medical University  Beijing P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Beijing Tiantan Hospital Capital Medical University  Beijing P. R. China"},{"name":"Department of Clinical Pharmacology, College of Pharmaceutical Sciences Capital Medical University  Beijing Beijing P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0281-2259","authenticated-orcid":false,"given":"Zhigang","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Beijing Tiantan Hospital Capital Medical University  Beijing P. R. China"},{"name":"Department of Clinical Pharmacology, College of Pharmaceutical Sciences Capital Medical University  Beijing Beijing P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1385-4315","authenticated-orcid":false,"given":"Shenghui","family":"Mei","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Beijing Tiantan Hospital Capital Medical University  Beijing P. R. China"},{"name":"Department of Clinical Pharmacology, College of Pharmaceutical Sciences Capital Medical University  Beijing Beijing P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,12]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.21873\/invivo.12487"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchromb.2016.10.035"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsps.2014.03.002"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/onco.13603"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/FTD.0000000000000434"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/chromsci\/bmt081"},{"issue":"4","key":"e_1_2_8_8_1","first-page":"395","article-title":"HPLC determination of methotrexate and its metabolite in serum","volume":"37","author":"Brandsteterov\u00e1 E.","year":"1990","journal-title":"Neoplasma"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1177\/00045632221077183"},{"issue":"8","key":"e_1_2_8_10_1","first-page":"1373","article-title":"Development and validation of HPLC method to determination of methotrexate in children oncologic patients","volume":"19","author":"De Abreu C. C.","year":"2015","journal-title":"European Review for Medical and Pharmacological Sciences"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.2147\/DDDT.S335122"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpdd.279"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpba.2022.115034"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.2015-0164"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12911-023-02248-7"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00280-019-03966-4"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/jms.4648"},{"issue":"7","key":"e_1_2_8_18_1","first-page":"599","article-title":"The influence of 7\u2010OH methotrexate metabolite on clinical relevance of methotrexate determination","volume":"57","author":"Klapkova E.","year":"2011","journal-title":"Clinical Laboratory"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpba.2021.114380"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchromb.2015.08.017"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.2147\/DDDT.S271568"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11033-020-05481-9"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1177\/00045632211031284"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xphs.2018.01.004"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpba.2018.06.011"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/bmc.3849"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1080\/10826076.2016.1243558"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-3252-8_23"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchromb.2015.08.025"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2018.09.027"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/bmc.3408"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/jssc.202001081"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/751703"}],"container-title":["Biomedical Chromatography"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bmc.5789","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T20:06:14Z","timestamp":1760040374000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/bmc.5789"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12]]},"references-count":32,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2024,2]]}},"alternative-id":["10.1002\/bmc.5789"],"URL":"https:\/\/doi.org\/10.1002\/bmc.5789","archive":["Portico"],"relation":{},"ISSN":["0269-3879","1099-0801"],"issn-type":[{"value":"0269-3879","type":"print"},{"value":"1099-0801","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,12]]},"assertion":[{"value":"2023-10-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-11-06","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-12-01","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e5789"}}