Cocaethylene is an active metabolite produced when cocaine is consumed jointly with ethanol. The development of analytical techniques for determining cocaethylene and other cocaine metabolites is highly relevant for pharmacokinetic and toxicology studies of the cocaine and alcohol interaction in humans. The gas chromatography/mass spectrometry (GC/MS) method here reported is based on a single solid-phase extraction together with deuterated internal standards previously added to urine, followed by derivatization with pentafluoropropionic anhydride (hydroxyl and amine functions) and 1,1,1,3,3,3 hexafluor-2-propanol (carboxylic acid function) and injection into a capillary GC system coupled to a mass spectrometric detector in the selected ion monitoring acquisition mode. A sensitivity of 1-2 ng ml-1 for the quantitative analysis of cocaine and its main metabolites (ecgonine methyl ester, benzoylecgonine, cocaethylene and norcocaine) was achieved. In addition, some other minor metabolites were easily extracted and detected.