To the Editor:
During the development of a routine workplace drug testing of urine with CEDIA Amphetamine reagent, two urines with a positive result were found. One result was clearly above the established cutoff (586 vs. 500), and the other was slightly below the cutoff (494 vs. 500). We proceeded to extract the urines (2 mL urine + amphetamine and methylendioxiamphetamine deuterated internal standards + borate buffer [pH 9] + dichloromethane/isopropanol [85:15] in Bond Elut) and analyze the extracts by gas chromatography with nitrogen-phosphorus detection (GC–NPD) and gas chromatography–mass spectrometry (GC–MS). Neither urine contained amphetamine or amphetamine derivatives. However, both urines were found to contain chloroquine (213.29 mg/mL and 72 mg/mL) and its main metabolite, desethylchloroquine (56.50 mg/mL and 4.10 mg/mL).

We prepared urines spiked with different concentrations of chloroquine and tested them on the Hitachi 902 Automatic Analyzer using CEDIA Amphetamine reagent. We found that chloroquine was responsible for the positive results when at high concentrations. Table I shows the different concentrations of chloroquine assayed and its results as compared with the established cutoff for amphetamine reagent (500).

We could not prepare spiked urines with the metabolite because we did not have a reference standard (desethylchloroquine in the urines was calculated by GC–NPD using chloroquine as standard), but it is likely to give similar or more (considering its molecular formula) cross-reactivity than chloroquine itself. Thus, the positive result in urines is due to chloroquine, its metabolite desethylchloroquine, and probably some other minor metabolites. This could explain the result, in the assay, of the second urine in spite of its concentration of chloroquine (73 mg/mL) below 100 mg/mL.

Chloroquine is an antibacterial drug that is effective for the profilaxis of P. falciparum in some geographical areas (A zone of OMS classification) where the Plasmodium has not developed resistance. It is used in relatively high doses, thus making possible the elimination of high concentrations of the drug in urine.