Stereoselective method to quantify bupropion and its three major metabolites, hydroxybupropion, erythro-dihydrobupropion, and threo-dihydrobupropion using HPLC-MS/MS

dc.contributor.authorMasters, Andrea R.
dc.contributor.authorMcCoy, Michael
dc.contributor.authorJones, David R.
dc.contributor.authorDesta, Zeruesenay
dc.contributor.departmentDepartment of Medicine, IU School of Medicineen_US
dc.date.accessioned2017-07-26T16:09:33Z
dc.date.available2017-07-26T16:09:33Z
dc.date.issued2016-03-15
dc.description.abstractBupropion metabolites formed via oxidation and reduction exhibit pharmacological activity, but little is known regarding their stereoselective disposition. A novel stereoselective liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed to separate and quantify enantiomers of bupropion, 4-hydroxybupropion, and erythro- and threo-dihydrobupropion. Liquid-liquid extraction was implemented to extract all analytes from 50 μL human plasma. Acetaminophen (APAP) was used as an internal standard. The analytes were separated on a Lux 3 μ Cellulose-3 250×4.6 mm column by methanol: acetonitrile: ammonium bicarbonate: ammonium hydroxide gradient elution and monitored using an ABSciex 5500 QTRAP triple-quadrupole mass spectrometer equipped with electrospray ionization probe in positive mode. Extraction efficiency for all analytes was ≥70%. The stability at a single non-extracted concentration for over 48 h at ambient temperature resulted in less than 9.8% variability for all analytes. The limit of quantification (LOQ) for enantiomers of bupropion and 4-hydroxybupropion was 0.3 ng/mL, while the LOQ for enantiomers of erythro- and threo-hydrobupropion was 0.15 ng/mL. The intra-day precision and accuracy estimates for enantiomers of bupropion and its metabolites ranged from 3.4% to 15.4% and from 80.6% to 97.8%, respectively, while the inter-day precision and accuracy ranged from 6.1% to 19.9% and from 88.5% to 99.9%, respectively. The current method was successfully implemented to determine the stereoselective pharmacokinetics of bupropion and its metabolites in 3 healthy volunteers administered a single 100mg oral dose of racemic bupropion. This novel, accurate, and precise HPLC-MS/MS method should enhance further research into bupropion stereoselective metabolism and drug interactions.en_US
dc.eprint.versionAuthor's manuscripten_US
dc.identifier.citationMasters, A. R., McCoy, M., Jones, D. R., & Desta, Z. (2016). Stereoselective method to quantify bupropion and its three major metabolites, hydroxybupropion, erythro-dihydrobupropion, and threo-dihydrobupropion using HPLC-MS/MS. Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences, 1015-1016, 201–208. http://doi.org/10.1016/j.jchromb.2016.02.018en_US
dc.identifier.urihttps://hdl.handle.net/1805/13594
dc.language.isoen_USen_US
dc.publisherElsevieren_US
dc.relation.isversionof10.1016/j.jchromb.2016.02.018en_US
dc.relation.journalJournal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciencesen_US
dc.rightsPublisher Policyen_US
dc.sourcePMCen_US
dc.subject4-Hydroxybupropionen_US
dc.subjectBupropionen_US
dc.subjectEnantiomersen_US
dc.subjectHPLC–MS/MSen_US
dc.subjectStereoselectiveen_US
dc.subjecterythro-Dihydrobupropionen_US
dc.subjectthreo-Dihydrobupropionen_US
dc.titleStereoselective method to quantify bupropion and its three major metabolites, hydroxybupropion, erythro-dihydrobupropion, and threo-dihydrobupropion using HPLC-MS/MSen_US
dc.typeArticleen_US
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