{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T15:28:10Z","timestamp":1789140490334,"version":"build-2803163510"},"reference-count":16,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,8]]},"abstract":"<jats:sec>\n            <jats:title>Background:<\/jats:title>\n            <jats:p>Therapeutic drug monitoring of antiepileptic drugs (AEDs) is often necessary to prevent associated destructive toxicities. Tandem mass spectrometry (MS\/MS) with stable-isotope\u2013labeled internal standards is considered the gold standard for the measurement of AEDs. This study presents the development and validation of a clinical ultra-performance liquid chromatography\u2013MS\/MS method for the concurrent measurement of gabapentin, lamotrigine, levetiracetam, monohydroxy derivative of oxcarbazepine, and zonisamide in human serum.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods:<\/jats:title>\n            <jats:p>To determine the optimal assay analyte range, one year of AED therapeutic drug monitoring results (n = 1825) were evaluated. Simple protein precipitation with acetonitrile containing isotopically labeled internal standards was used. Reverse-phase ultra-performance liquid chromatography chromatographic separation was used, having a total run time of 3 minutes. Quantification of analytes was accomplished using electrospray ionization in positive ion mode and collision-induced dissociation MS. Assay parameters were evaluated per Food and Drug Administration bioanalytical guidelines.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results:<\/jats:title>\n            <jats:p>After evaluating internal patient data, the analytical measuring range (AMR) of the assay was established as 0.1\u2013100 mcg\/mL. All AEDs were linear across the AMR, with R<jats:sup>2<\/jats:sup> values ranging from 0.9988 to 0.9999. Imprecision (% coefficient of variation) and inaccuracy (% difference) were calculated to be &lt;20% for the lower limit of quantitation and &lt;15% for the low, mid, and high levels of quality controls across the AMR. All AEDs demonstrated acceptable assay parameters for carryover, stability under relevant storage conditions, matrix effects, recovery, and extraction and processing efficiency. In addition, the assay displayed acceptable concordance to results obtained from a national reference laboratory, with Deming regression R<jats:sup>2<\/jats:sup> of 0.99 and slope values ranging from 0.89 to 1.17.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>A simple, cost-effective, and robust ultra-performance liquid chromatography\u2013tandem mass spectrometry method for monitoring multiple AEDs was developed and validated to address the clinical needs of patients at our institution.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1097\/ftd.0000000000000516","type":"journal-article","created":{"date-parts":[[2018,4,6]],"date-time":"2018-04-06T13:24:58Z","timestamp":1523021098000},"page":"469-476","source":"Crossref","is-referenced-by-count":30,"title":["Development and Validation of an Ultra-Performance Liquid Chromatography\u2013Tandem Mass Spectrometry Method for the Concurrent Measurement of Gabapentin, Lamotrigine, Levetiracetam, Monohydroxy Derivative of Oxcarbazepine, and Zonisamide Concentrations in Serum in a Clinical Setting"],"prefix":"10.1097","volume":"40","author":[{"given":"Michael J.","family":"Palte","sequence":"first","affiliation":[{"name":"Department of Pathology, Brigham and Women's Hospital and Harvard Medical School;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sankha S.","family":"Basu","sequence":"additional","affiliation":[{"name":"Department of Pathology, Brigham and Women's Hospital and Harvard Medical School;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jameson L.","family":"Dahlin","sequence":"additional","affiliation":[{"name":"Department of Pathology, Brigham and Women's Hospital and Harvard Medical School;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralitsa","family":"Gencheva","sequence":"additional","affiliation":[{"name":"Department of Pathology, Brigham and Women's Hospital, Boston, MA; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donald","family":"Mason","sequence":"additional","affiliation":[{"name":"Waters Corporation, Milford, MA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petr","family":"Jarolim","sequence":"additional","affiliation":[{"name":"Department of Pathology, Brigham and Women's Hospital and Harvard Medical School;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Athena K.","family":"Petrides","sequence":"additional","affiliation":[{"name":"Department of Pathology, Brigham and Women's Hospital and Harvard Medical School;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"R2-20230814","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1177\/2042098611411127","article-title":"New generation antiepileptic drugs: what do they offer in terms of improved tolerability and 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two active metabolites in whole blood by reversed phase UPLC-MS\/MS and some examples of application of the method in forensic toxicology cases","volume":"7","author":"Karinen","year":"2015","journal-title":"Drug Test Anal."},{"key":"R13-20230814","doi-asserted-by":"crossref","first-page":"1519","DOI":"10.1002\/bmc.2726","article-title":"Detection of 22 antiepileptic drugs by ultra-performance liquid chromatography coupled with tandem mass spectrometry applicable to routine therapeutic drug monitoring","volume":"26","author":"Shibata","year":"2012","journal-title":"Biomed Chromatogr."},{"key":"R14-20230814","doi-asserted-by":"crossref","first-page":"2053","DOI":"10.1002\/bmc.3789","article-title":"Simultaneous determination of four antiepileptic drugs in human plasma samples using an ultra-high-performance liquid chromatography tandem mass spectrometry method and its application in therapeutic drug monitoring","volume":"30","author":"Dupouey","year":"2016","journal-title":"Biomed 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Med."},{"key":"R20-20230814","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1093\/chromsci\/42.7.383","article-title":"Evaluation of deuterium isotope effects in normal-phase LC-MS-MS separations using a molecular modeling approach","volume":"42","author":"Iyer","year":"2004","journal-title":"J Chromatogr Sci."}],"container-title":["Therapeutic Drug 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