DETERMINATION OF THE STEREOISOMERS OF HYDROXYCHLOROQUINE AND ITS MAJOR METABOLITES IN PLASMA AND URINE FOLLOWING A SINGLE ORAL-ADMINISTRATION OF RACEMIC HYDROXYCHLOROQUINE

Plaquenil (hydroxychloroquine, HCQ; Sanofi Winthrop Pharmaceuticals, New York, NY) is a stereoisomeric drug administered as a racemic (50: 50) mixture of two isomeric forms—(+) and (-) HCQ. To correlate clinical efficiency accurately with dose, it is necessary to determine the fate of both isomers. This will allow for the optimization of clinical dosing. A method has been developed for the quantitation of (+) and (-) HCQ and its major metabolites, desethylhydroxychloroquine (DHCQ), desethylchloroquine (DCQ), and bisdes-ethylchloroquine (BDCQ), in plasma and in urine. Application of this method in a preliminary study in four human volunteers is reported. After a single oral dose of 200 mg of Plaquenil, the average enantiomeric ratio of (+) to (-) HCQ was approximately 1 over an 8-hour period. However, the average cumulative 48-hour excretion of HCQ, DHCQ, and DCQ showed steroselective excretion. © 1993, W.B. Saunders Company. All rights reserved.