{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T19:59:24Z","timestamp":1760385564964},"reference-count":11,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,8]]},"abstract":"<jats:sec>\n            <jats:title>Background:<\/jats:title>\n            <jats:p>Valproic acid (VPA) is a widely prescribed medicine, and acute toxicity is possible. As such, it should be included in any nontargeted urine drug screening method. In many published liquid chromatography\u2013electrospray ionization\u2013mass spectrometry (LC\u2013ESI\u2013MS\/MS) methods, VPA is usually measured using a pseudo-multiple reaction monitoring (MRM) transition. We investigate a simple ultra-high-performance liquid chromatography\u2013quadrupole time-of-flight (QTof) approach to detect the presence of VPA with more confidence.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods:<\/jats:title>\n            <jats:p>Three commercially sourced VPA metabolites were characterized and added to a nontargeted high-resolution MS urine drug screening method. All analyses were performed on a Waters Xevo G2-XS LC-QTof in negative electrospray ionization mode. The mass detector was operated in MS<jats:sup>E<\/jats:sup> mode, and data were processed with UNIFI software. Sixty-eight patient urine samples, which were previously identified by a well-established gas chromatography\u2013MS method as containing VPA, were analyzed on the Waters Xevo G2-XS LC-QTof, to validate this approach.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results:<\/jats:title>\n            <jats:p>VPA metabolite standards were characterized, and their detection data were added to the broad drug screening library. VPA metabolites were readily detectable in the urine of patients taking VPA.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>The inclusion of characterized VPA metabolites provides a simple and reliable method enabling the detection of VPA in nontargeted urine drug screening.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1097\/ftd.0000000000000417","type":"journal-article","created":{"date-parts":[[2017,5,17]],"date-time":"2017-05-17T13:53:07Z","timestamp":1495029187000},"page":"457-460","source":"Crossref","is-referenced-by-count":8,"title":["Challenges for Detecting Valproic Acid in a Nontargeted Urine Drug Screening Method"],"prefix":"10.1097","volume":"39","author":[{"given":"Jeffrey D.","family":"Pope","sequence":"first","affiliation":[{"name":"Clinical Biochemistry, Alfred Pathology Service, Alfred Health;"},{"name":"Department of Forensic Medicine, Monash University;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marion J.","family":"Black","sequence":"additional","affiliation":[{"name":"Clinical Biochemistry, Alfred Pathology Service, Alfred Health;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olaf H.","family":"Drummer","sequence":"additional","affiliation":[{"name":"Department of Forensic Medicine, Monash University;"},{"name":"Victorian Institute of Forensic Medicine; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hans G.","family":"Schneider","sequence":"additional","affiliation":[{"name":"Clinical Biochemistry, Alfred Pathology Service, Alfred Health;"},{"name":"Central Clinical School, Monash University, Melbourne, Australia."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"R1-20230814","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1016\/j.jflm.2011.06.003","article-title":"An UPLC-MS\/MS method for the determination of valproic acid in blood of a fatal intoxication case","volume":"18","author":"Proenca","year":"2011","journal-title":"J Forensic Leg Med."},{"key":"R2-20230814","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1212\/WNL.46.2.465","article-title":"Valproic acid hepatic fatalities. 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U.S. experience since 1986","volume":"46","author":"Bryant","year":"1996","journal-title":"Neurology"},{"key":"R3-20230814","doi-asserted-by":"crossref","first-page":"1939","DOI":"10.1016\/j.jchromb.2011.05.022","article-title":"LC-MS\/MS method for simultaneous determination of valproic acid and major metabolites in human plasma","volume":"879","author":"Gao","year":"2011","journal-title":"J Chromatogr B Analyt Technol Biomed Life Sci."},{"key":"R4-20230814","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.jpha.2015.11.006","article-title":"Liquid chromatography\u2013tandem mass spectrometry method for simultaneous determination of valproic acid and its ene-metabolites in epilepsy patient plasma","volume":"6","author":"Lu","year":"2016","journal-title":"J Pharm Anal."},{"key":"R5-20230814","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1016\/j.clinbiochem.2016.07.005","article-title":"Quality management in clinical application of mass spectrometry measurement systems","volume":"49","author":"Vogeser","year":"2016","journal-title":"Clin Biochem."},{"key":"R6-20230814","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1002\/bmc.1130060108","article-title":"Quantitative determination of valproic acid and 14 metabolites in serum and urine by gas chromatography\/mass spectrometry","volume":"6","author":"Fisher","year":"1992","journal-title":"Biomed Chromatogr."},{"key":"R7-20230814","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1248\/bpb.21.304","article-title":"Urinary metabolites of valproic acid in epileptic patients","volume":"21","author":"Katayama","year":"1998","journal-title":"Biol Pharm Bull."},{"key":"R8-20230814","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1248\/bpb.22.716","article-title":"Valproic acid elimination rate and urinary excretion of its glucuronide conjugate in patients with epilepsy","volume":"22","author":"Yoshida","year":"1999","journal-title":"Biol Pharm Bull."},{"key":"R9-20230814","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1093\/jat\/bks084","article-title":"Validation of LC\u2013TOF-MS screening for drugs, metabolites, and collateral compounds in forensic toxicology specimens","volume":"37","author":"Guale","year":"2013","journal-title":"J Anal Toxicol."},{"key":"R10-20230814","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1093\/jat\/bkt083","article-title":"Screening and confirmation of 62 drugs of abuse and metabolites in urine by ultra-high-performance liquid chromatography\u2013quadrupole time-of-flight mass spectrometry","volume":"37","author":"Tsai","year":"2013","journal-title":"J Anal Toxicol."},{"key":"R11-20230814","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.1373\/clinchem.2014.222976","article-title":"Liquid chromatography high-resolution TOF analysis: investigation of MSE for broad-spectrum drug screening","volume":"60","author":"Chindarkar","year":"2014","journal-title":"Clin Chem."}],"container-title":["Therapeutic Drug Monitoring"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.lww.com\/00007691-201708000-00024","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,14]],"date-time":"2023-08-14T22:12:08Z","timestamp":1692051128000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.lww.com\/00007691-201708000-00024"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,8]]},"references-count":11,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2017]]}},"URL":"https:\/\/doi.org\/10.1097\/ftd.0000000000000417","relation":{},"ISSN":["0163-4356"],"issn-type":[{"value":"0163-4356","type":"print"}],"subject":[],"published":{"date-parts":[[2017,8]]}}}