Urinary metabolism of chloroquine.

For reinvestigation of the metabolism of 7-chloro-4-(4-diethylamino-1-methylbutylamino)quinoline (chloroquine, Resochin), urine samples from patients and volunteers with single or repeated chloroquine doses were collected and analyzed by gas chromatography, thin-layer chromatography, and gas chromatography/mass spectrometry. Furthermore, urine samples from two cases of chloroquine overdose were included in the study. Three previously unknown metabolites could be identified in nearly all samples, although they amounted to less than 2% of the concentration of unchanged chloroquine in the urine. However, in those samples with failure of detection, the chloroquine urine levels were already so low that metabolite concentrations were beyond the limit of detection of the analytical method. Altogether, the study gave no evidence for a dose-dependent formation of the three previously unknown metabolites. Besides the new metabolites, an artifact generated from chloroquine-N-oxide could be characterized by gas chromatography/mass spectrometry. However, the formation of a further chloroquine metabolite with an alcohol function which has been described in the literature could not be confirmed.