{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T22:25:11Z","timestamp":1772749511752,"version":"3.50.1"},"reference-count":31,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2022,9,2]],"date-time":"2022-09-02T00:00:00Z","timestamp":1662076800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Department of Science and Technology of Jilin Province","award":["20210203068SF"],"award-info":[{"award-number":["20210203068SF"]}]},{"name":"Department of Science and Technology of Jilin Province","award":["JDYY2021-A0009"],"award-info":[{"award-number":["JDYY2021-A0009"]}]},{"name":"Department of Science and Technology of Jilin Province","award":["JLSWSRCZX221-056"],"award-info":[{"award-number":["JLSWSRCZX221-056"]}]},{"name":"Department of Science and Technology of Jilin Province","award":["20200404167YY"],"award-info":[{"award-number":["20200404167YY"]}]},{"name":"First Hospital of Jilin University","award":["20210203068SF"],"award-info":[{"award-number":["20210203068SF"]}]},{"name":"First Hospital of Jilin University","award":["JDYY2021-A0009"],"award-info":[{"award-number":["JDYY2021-A0009"]}]},{"name":"First Hospital of Jilin University","award":["JLSWSRCZX221-056"],"award-info":[{"award-number":["JLSWSRCZX221-056"]}]},{"name":"First Hospital of Jilin University","award":["20200404167YY"],"award-info":[{"award-number":["20200404167YY"]}]},{"name":"Finance Department of Jilin Province","award":["20210203068SF"],"award-info":[{"award-number":["20210203068SF"]}]},{"name":"Finance Department of Jilin Province","award":["JDYY2021-A0009"],"award-info":[{"award-number":["JDYY2021-A0009"]}]},{"name":"Finance Department of Jilin Province","award":["JLSWSRCZX221-056"],"award-info":[{"award-number":["JLSWSRCZX221-056"]}]},{"name":"Finance Department of Jilin Province","award":["20200404167YY"],"award-info":[{"award-number":["20200404167YY"]}]},{"name":"Project of Jilin Provincial Department of science and technology","award":["20210203068SF"],"award-info":[{"award-number":["20210203068SF"]}]},{"name":"Project of Jilin Provincial Department of science and technology","award":["JDYY2021-A0009"],"award-info":[{"award-number":["JDYY2021-A0009"]}]},{"name":"Project of Jilin Provincial Department of science and technology","award":["JLSWSRCZX221-056"],"award-info":[{"award-number":["JLSWSRCZX221-056"]}]},{"name":"Project of Jilin Provincial Department of science and technology","award":["20200404167YY"],"award-info":[{"award-number":["20200404167YY"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>A sensitive and rapid bioanalytical method based on the LC-triple-stage fragmentation (LC-MS3) strategy on a hybrid triple quadrupole-linear ion trap mass spectrometer in combination with protein precipitation extraction for sample pretreatment has been developed and validated for the simultaneous determination of the antiepileptic drug oxcarbazepine (OXC) and its main active metabolite (MHD) in human serum. The separation was performed on a Waters XBridge BEH C18 column (2.5 \u00b5m, 2.1 \u00d7 50 mm) in isocratic elution with 0.1% formic acid in water and methanol (50:50, v:v) as the mobile phase. The run time for each sample was 2.0 min. The calibration curves ranging from 25 to 1600 ng\/mL for OXC and from 0.5 to 32 \u03bcg\/mL for MHD showed correlation coefficients (r) better than 0.99. All of the validation data, such as precision, accuracy and other parameters, fit the requirements of the current bioanalytical method validation guidelines. The LC-MS3 method for quantitation of OXC and MHD was compared with the LC-MRM based method. Passing\u2013Bablok regression coefficients and Bland\u2013Altman plots showed that the developed LC\u2013MS3 method is a reliable method for quantitative analysis of OXC and MHD. The proposed LC-MS3 method was successfully applied to determine the serum concentrations of OXC and MHD to support a clinical study.<\/jats:p>","DOI":"10.3390\/molecules27175670","type":"journal-article","created":{"date-parts":[[2022,9,7]],"date-time":"2022-09-07T01:51:57Z","timestamp":1662515517000},"page":"5670","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Development and Validation of a Highly Sensitive and Rapid LC-MS3 Strategy to Determine Oxcarbazepine and Its Active Metabolite in the Serum of Patients with Epilepsy and Its Application in Therapeutic Drug Monitoring"],"prefix":"10.3390","volume":"27","author":[{"given":"Zhengchao","family":"Ji","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine, The First Hospital of Jilin University, Jilin University, Changchun 130021, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tingting","family":"Li","sequence":"additional","affiliation":[{"name":"Vascular Surgery, General Surgery Center, The First Hospital of Jilin University, Jilin University, Changchun 130021, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xin","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Health Examination Center, The First Hospital of Jilin University, Jilin University, Changchun 130021, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, The First Hospital of Jilin University, Jilin University, Changchun 130021, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanyan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, The First Hospital of Jilin University, Jilin University, Changchun 130021, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, The First Hospital of Jilin University, Jilin University, Changchun 130021, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.jchromb.2007.10.025","article-title":"Development and validation of a LC\/MS\/MS method for simultaneous quantification of oxcarbazepine and its main metabolites in human serum","volume":"860","author":"Paglia","year":"2007","journal-title":"J. Chromatogr. B Analyt. Technol. Biomed. Life Sci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.1124\/dmd.109.030593","article-title":"Pharmacokinetics of the monohydroxy derivative of oxcarbazepine and its enantiomers after a single intravenous dose given as racemate compared with a single oral dose of oxcarbazepine","volume":"39","author":"Flesch","year":"2011","journal-title":"Drug Metab. Dispos."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"137","DOI":"10.2165\/00023210-200115020-00005","article-title":"Oxcarbazepine: An update of its efficacy in the management of epilepsy","volume":"15","author":"Wellington","year":"2001","journal-title":"CNS Drugs"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1016\/j.braindev.2008.01.007","article-title":"New antiepileptic drugs in pediatric epilepsy","volume":"30","author":"Hwang","year":"2008","journal-title":"Brain Dev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"S2","DOI":"10.1111\/j.1528-1157.1999.tb00913.x","article-title":"Comparative anticonvulsant and mechanistic profile of the established and newer antiepileptic drugs","volume":"40","author":"White","year":"1999","journal-title":"Epilepsia"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1016\/S0149-2918(01)80019-9","article-title":"Oxcarbazepine, an antiepileptic agent","volume":"23","author":"Kalis","year":"2001","journal-title":"Clin Ther."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"185","DOI":"10.2165\/00044011-200424040-00001","article-title":"Overview of the clinical pharmacokinetics of oxcarbazepine","volume":"24","author":"Flesch","year":"2004","journal-title":"Clin. Drug Investig."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/j.jchromb.2005.12.003","article-title":"Use of microbore LC-MS\/MS for the quantification of oxcarbazepine and its active metabolite in rat brain microdialysis samples","volume":"831","author":"Lanckmans","year":"2006","journal-title":"J. Chromatogr. B Analyt. Technol. Biomed. Life Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1002\/bmc.1510","article-title":"Rapid ultraperformance liquid chromatography-tandem mass spectrometry method for quantification of oxcarbazepine and its metabolite in human plasma","volume":"25","author":"Bhatt","year":"2011","journal-title":"Biomed. Chromatogr."},{"key":"ref_10","first-page":"508","article-title":"Update on Antiepileptic Drugs_2019","volume":"25","year":"2019","journal-title":"Continuum"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1111\/j.1528-1167.2008.01561.x","article-title":"Antiepileptic drugsbest practice guidelines for therapeutic drug monitoring: A position paper by the subcommission on therapeutic drug monitoring, ILAE Commission on Therapeutic Strategies","volume":"49","author":"Patsalos","year":"2008","journal-title":"Epilepsia"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.seizure.2015.07.018","article-title":"Relationship between mono-hydroxy-carbazepine serum concentrations and adverse effects in patients on oxcarbazepine monotherapy","volume":"31","author":"Sattler","year":"2015","journal-title":"Seizure"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"6370","DOI":"10.1038\/s41598-021-85920-0","article-title":"Population pharmacokinetic model development and its relationship with adverse events of oxcarbazepine in adult patients with epilepsy","volume":"11","author":"Jang","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1016\/S0731-7085(01)00684-7","article-title":"LC determination of oxcarbazepine and its active metabolite in human serum","volume":"28","author":"Levert","year":"2002","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1097\/FTD.0b013e3181c324c8","article-title":"A novel HPLC method for quantification of 10 antiepileptic drugs or metabolites in serumplasma using a monolithic column","volume":"32","author":"Heideloff","year":"2010","journal-title":"Ther. Drug Monit."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1097\/00007691-200406000-00014","article-title":"Feasibility and limitations of oxcarbazepine monitoring using salivary monohydroxycarbamazepine (MHD)","volume":"26","author":"Miles","year":"2004","journal-title":"Ther. Drug Monit."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/S1570-0232(02)00664-5","article-title":"Liquid chromatographic determination of oxcarbazepine and its metabolites in plasma of epileptic patients after solid-phase extraction","volume":"783","author":"Mandrioli","year":"2003","journal-title":"J. Chromatogr. B Anal. Technol. Biomed. Life Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1429","DOI":"10.1515\/CCLM.2008.276","article-title":"Measurement of 10,11-dihydro-10-hydroxy-carbamazepine in serum and plasma by high-performance liquid chromatography","volume":"46","author":"Hunek","year":"2008","journal-title":"Clin. Chem. Lab. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2970","DOI":"10.1002\/jssc.201200439","article-title":"A novel microextraction by packed sorbent-gas chromatography procedure for the simultaneous analysis of antiepileptic drugs in human plasma and urine","volume":"35","author":"Rani","year":"2012","journal-title":"J. Sep. Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e4915","DOI":"10.1002\/bmc.4915","article-title":"Accurate and simple determination of oxcarbazepine in human plasma and urine samples using switchable-hydrophilicity solvent in GC\u2013MS","volume":"34","author":"Erarpat","year":"2020","journal-title":"Biomed. Chromatogr."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1016\/j.jpba.2017.11.041","article-title":"Analysis of unbound plasma concentration of oxcarbazepine and the 10-hydroxycarbazepine enantiomers by liquid chromatography with tandem mass spectrometry in healthy volunteers","volume":"149","author":"Antunes","year":"2018","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1002\/dta.1733","article-title":"Determination of a selection of anti-epileptic drugs and 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":"ref_23","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1093\/jat\/bkaa095","article-title":"A Rapid LC\u2013MS-MS Method for the Quantitation of Antiepileptic Drugs in Urine","volume":"44","author":"Feng","year":"2020","journal-title":"J. Anal. Toxicol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"964","DOI":"10.1002\/jssc.201501067","article-title":"Simultaneous determination of ten antiepileptic drugs in human plasma by liquid chromatography and tandem mass spectrometry with positive\/negative ion-switching electrospray ionization and its application in therapeutic drug monitoring","volume":"39","author":"Yin","year":"2016","journal-title":"J. Sep. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Farouk, F., ElKady, E.F., and Azzazy, H.M.E. (2017). Simultaneous UPLC-MS\/MS determination of antiepileptic agents for dose adjustment. Biomed. Chromatogr., 31.","DOI":"10.1002\/bmc.3921"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"4478","DOI":"10.1039\/D1AY01372F","article-title":"A LC-MS(3) strategy to determine lamotrigine by Q-Q-trap tandem mass spectrometry coupled with triple stage fragmentation to enhance sensitivity and selectivity","volume":"13","author":"Shi","year":"2021","journal-title":"Anal. Methods"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"5605","DOI":"10.1007\/s00216-019-01941-9","article-title":"A combined LC-MS\/MS and LC-MS3 multi-method for the quantification of iodothyronines in human blood serum","volume":"411","author":"Richards","year":"2019","journal-title":"Anal. Bioanal. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Ma, D., Ji, Z., Cao, H., Huang, J., Zeng, L., and Yin, L. (2022). LC-MS(3) Strategy for Quantification of Carbamazepine in Human Plasma and Its Application in Therapeutic Drug Monitoring. Molecules, 27.","DOI":"10.3390\/molecules27041224"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Ji, Z., Yin, L., Li, Y., Yang, X., Lin, L., Liu, L., Jiang, Y., and Huang, J. (2021). Development and validation of a liquid chromatography tandem mass spectrometry method with triple stage fragmentation to determine levetiracetam in epileptic patient serum and its application in therapeutic drug monitoring. J. Sep. Sci., 4255\u20134263.","DOI":"10.1002\/jssc.202100639"},{"key":"ref_30","unstructured":"Food and Drug Administration (2018). Guidance for Industry: Boianalytical Method Validation."},{"key":"ref_31","unstructured":"Chinese Pharmacopoeia Commission (2015). Pharmacopoeia of the People Republic of China (Volume Four)."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/27\/17\/5670\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:22:39Z","timestamp":1760142159000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/27\/17\/5670"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,2]]},"references-count":31,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2022,9]]}},"alternative-id":["molecules27175670"],"URL":"https:\/\/doi.org\/10.3390\/molecules27175670","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,2]]}}}