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dc.contributor.authorMoreno-Vicente, Raquel
dc.contributor.authorFernandez-Nieva, Zuriñe
dc.contributor.authorNavarro-Alvarez, Arantza
dc.contributor.authorGascon-Crespi, Irene
dc.contributor.authorFarre-Albaladejo, Magi
dc.contributor.authorIgartua, Manuela
dc.contributor.authorHernandez, Rosa Maria
dc.contributor.authorPedraz, Jose Luis
dc.date.accessioned2016-06-21T11:31:37Z
dc.date.available2016-06-21T11:31:37Z
dc.date.issued2015-10-10
dc.identifier.citationJournal of Pharmaceutical and Biomedical Analysis, Volume 114, 10 October 2015, Pages 105–112en
dc.identifier.issn0731-7085en
dc.identifier.urihttp://hdl.handle.net/11556/258
dc.description.abstractA bioanalytical method using high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) was developed and validated for simultaneous quantification of heroin, its main metabolites and naloxone. In addition, naltrexone was detected qualitatively. This method was used to analyse human plasma samples from a clinical trial after oral administration of a heroin/naloxone formulation in healthy volunteers. O-methylcodeine was used as an internal standard. Samples were kept in an ice-bath during their processing to minimize the degradation of heroin. A short methodology based on protein precipitation with methanol was used for sample preparation. After protein precipitation, only the addition of a formic acid solution was needed to elute heroin, 6-monoacetylmorphine, morphine, naloxone and naltrexone. Morphine metabolites were evaporated to dryness and reconstituted in a formic acid solution. Chromatographic separation was achieved at 35 C on an X-Bridge Phenyl column (150 x 4.6 mm, 5 mu m) using a gradient elution with a mobile phase of ammonium formate buffer at pH 3.0 and formic acid in acetonitrile. The run time was 8 min. The analytes were monitored using a triple quadrupole mass spectrometer with positive electrospray ionization (ESI+) in multiple reaction monitoring (MRM) mode. The method was found to be linear in a concentration range of 10-2000 ng/mL for M3G and 10-1000 ng/mL for the rest of compounds. Quality controls showed accurate values between -3.6% and 4.0% and intra- and inter-day precisions were below 11.5% for all analytes. The overall recoveries were approximately 100% for all analytes including the internal standard. A rapid, specific, precise and simple method was developed for the determination of heroin, its metabolites, naloxone and naltrexone in human plasma. This method was successfully applied to a clinical trial in 12 healthy volunteers.en
dc.language.isoengen
dc.publisherELSEVIER SCIENCE BV, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDSen
dc.titleDevelopment and validation of a bioanalytical method for the simultaneous determination of heroin, its main metabolites, naloxone and naltrexone by LC–MS/MS in human plasma samples: Application to a clinical trial of oral administration of a heroin/naloxone formulationen
dc.typearticleen
dc.identifier.doi10.1016/j.jpba.2015.04.044en
dc.isiYesen
dc.rights.accessRightsembargoedAccessen
dc.subject.keywordsHeroinen
dc.subject.keywordsLC-MS/MSen
dc.subject.keywordsPlasmaen
dc.subject.keywordsValidationen
dc.subject.keywordsPharmacokineticen


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