Enantioselective determination of hydroxychloroquine and its major metabolites in urine and the observation of a reversal in the (+)/(-)-hydroxychloroquine ratio.
A sequential achiral-chiral high-performance liquid chromatographic system has been developed for the quantitation in urine of the enantiomers of hydroxychloroquine (HCQ), and of its 3 major metabolites, desethylhydroxychloroquine (DHCQ), desethylchloroquine (DCQ), and bisdesethylchloroquine (BDCQ). HCQ and its metabolites were separated and quantified on a cyano-bonded phase, and the enantiomeric ratios were determined using a Chiral-AGP chiral stationary phase. The assay validation and application of this method to a preliminary study in a human volunteer are presented. In this subject, the initial 0-4 h urine contained the 2 HCQ enantiomers in a ratio of (+)-HCQ:(-)-HCQ of 3:2; by the 2,064 h of the study, this ratio had reversed to (+)-HCQ:(-)-HCQ of 3:7.
Fieger
H
H
Department of Oncology, McGill University, Montreal General Hospital, Quebec, Canada.
Iredale
J
J
Wainer
I W
IW
D002738:Chloroquine / Q000031:analogs & derivatives / Q000737:chemistry / Q000652:urine; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D006801:Humans; D006886:Hydroxychloroquine / Q000737:chemistry / Q000378:metabolism* / Q000652:urine*; D013237:Stereoisomerism
D006886:Hydroxychloroquine; D002738:Chloroquine; C033490:N,N-dideethylchloroquine; C007278:desethylchloroquine