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Protein haptenation by these reactive metabolites may be a factor in abacavir\u2010induced toxic events.<\/jats:p><jats:p><jats:bold>EXPERIMENTAL APPROACH<\/jats:bold> The formation of <jats:italic>N<\/jats:italic>\u2010terminal valine adducts from the abacavir\u2010derived aldehydes was investigated in the haemoglobin of Wistar rats treated with eight daily doses (120\u2003mg\u00b7kg<jats:sup>\u22121<\/jats:sup>) of abacavir. The analyses were conducted by high\u2010performance liquid chromatography\u2010electrospray ionization\u2010tandem mass spectrometry upon comparison with synthetic standards.<\/jats:p><jats:p><jats:bold>KEY RESULTS<\/jats:bold> An <jats:italic>N<\/jats:italic>\u2010terminal valine haemoglobin adduct derived from an \u03b1,\u03b2\u2010unsaturated aldehyde metabolite of abacavir was identified <jats:italic>in vivo<\/jats:italic> for the first time.<\/jats:p><jats:p><jats:bold>CONCLUSIONS AND IMPLICATIONS<\/jats:bold> This preliminary work on abacavir metabolism provides the first unequivocal evidence for the formation of an \u03b1,\u03b2\u2010unsaturated aldehyde metabolite <jats:italic>in vivo<\/jats:italic> and of its ability to form haptens with proteins. The methodology described herein can be used to assess the formation of this metabolite in human samples and has the potential to become a valuable pharmacological tool for mechanistic studies of abacavir toxicity. In fact, the simplicity of the method suggests that the abacavir adduct with the <jats:italic>N<\/jats:italic>\u2010terminal valine of haemoglobin could be used to investigate abacavir\u2010induced toxicity for accurate risk\/benefit estimations.<\/jats:p>","DOI":"10.1111\/j.1476-5381.2012.02079.x","type":"journal-article","created":{"date-parts":[[2012,6,22]],"date-time":"2012-06-22T20:43:50Z","timestamp":1340397830000},"page":"1353-1361","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["<i>N<\/i>\u2010terminal valine adduct from the anti\u2010HIV drug abacavir in rat haemoglobin as evidence for abacavir metabolism to a reactive aldehyde <i>in 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