Development 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 formulation

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dc.contributor.authorMoreno-Vicente, Raquel
dc.contributor.authorFernández-Nieva, Zuriñe
dc.contributor.authorNavarro, Arantza
dc.contributor.authorGascón-Crespí, Irene
dc.contributor.authorFarré-Albaladejo, Magí
dc.contributor.authorIgartua, Manuela
dc.contributor.authorHernández, Rosa María
dc.contributor.authorPedraz, José Luis
dc.contributor.institutionDesarrollo Farmaceutico
dc.date.accessioned2024-07-24T12:04:10Z
dc.date.available2024-07-24T12:04:10Z
dc.date.issued2015-10-01
dc.descriptionPublisher Copyright: © 2015.
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. ×. 4.6. mm, 5. μm) 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.description.statusPeer reviewed
dc.format.extent8
dc.identifier.citationMoreno-Vicente , R , Fernández-Nieva , Z , Navarro , A , Gascón-Crespí , I , Farré-Albaladejo , M , Igartua , M , Hernández , R M & Pedraz , J L 2015 , ' Development 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 formulation ' , Journal of Pharmaceutical and Biomedical Analysis , vol. 114 , pp. 105-112 . https://doi.org/10.1016/j.jpba.2015.04.044
dc.identifier.doi10.1016/j.jpba.2015.04.044
dc.identifier.issn0731-7085
dc.identifier.urihttps://hdl.handle.net/11556/3425
dc.identifier.urlhttp://www.scopus.com/inward/record.url?scp=84930666868&partnerID=8YFLogxK
dc.language.isoeng
dc.relation.ispartofJournal of Pharmaceutical and Biomedical Analysis
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subject.keywordsHeroin
dc.subject.keywordsLC-MS/MS
dc.subject.keywordsPharmacokinetic
dc.subject.keywordsPlasma
dc.subject.keywordsValidation
dc.subject.keywordsAnalytical Chemistry
dc.subject.keywordsPharmaceutical Science
dc.subject.keywordsDrug Discovery
dc.subject.keywordsSpectroscopy
dc.subject.keywordsClinical Biochemistry
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.typejournal article
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