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Enantioselective Analysis of the Metabolites of Hydroxychloroquine and Application to an in Vitro Metabolic Study by Carmem Dickow Cardoso; Pierina Sueli Bonato is a Chemistry article available to read on EtoBox.

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A one-step chiral method for the quantification of the enantiomers of two hydroxychloroquine (HCQ) metabolites, desethylchloroquine (DCQ) and desethylhydroxychloroquine (DHCQ) by HPLC is described, in addition to its application to the in vitro study of HCQ metabolism in rat liver microsomes. Liquid-liquid extraction was used to extract the enantiomers from microsome samples and the separation was performed on a Chiralpak AD-RH column protected with an RP-8 guard column using hexane:isopropanol (92:8, v/v) plus 0.1% diethylamine as the mobile phase, at a flow rate of 1.0 mL min -1 . The detection was carried out at 343 nm. The method proved to be linear in the range of 50-5000 ng mL -1 for DCQ enantiomers and 125-2500 ng mL -1 for DHCQ enantiomers, with a quantification limit of 50 and 125 ng mL -1 , respectively. Precision and accuracy, demonstrated by within-day and between-day assays, were lower than 15%. The metabolic study demonstrated that metabolism is stereoselective for HCQ. The major metabolites formed in the incubation of racemic HCQ were (-)-(R)-DCQ and (-)-(R)-DHCQ with R/S ratios of 2.2 and 3.3, respectively.

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Author

Carmem Dickow Cardoso; Pierina Sueli Bonato

Publisher

Elsevier Science; Elsevier ; Elsevier BV (ISSN 0731-7085)

Published

2005

Language

EN

Field

Chemistry (Physical Sciences)