Determination of chloroquine and its major metabolite in blood using perfluoroacylation followed by fused-silica capillary gas chromatography with nitrogen-sensitive detection.

Tandem fused-silica capillary gas chromatographic methods for the determination of chloroquine and its major metabolite, desethylchloroquine, are described. Method A employs a single extraction step and internal standardization to permit rapid, precise analyses for chloroquine in whole blood. Method B, employing derivatization with pentafluoropropionic anhydride, can then be applied to the extract to allow qualitative and quantitative confirmation of chloroquine and sensitive, precise quantification for desethylchloroquine. The detection limit for chloroquine in blood is 5 ng/ml by both methods; the limit for desethylchloroquine is 15 ng/ml. Excellent precision is achieved by the methodology, partly due to the use of separate internal standards for the two analytes, each internal standard being a close analogue of the corresponding analyte. Data are presented which demonstrate the increase over time of metabolite relative to unchanged chloroquine found in the blood of a volunteer undergoing a chemoprophylactic regimen of chloroquine.