Urinary metabolism of chloroquine

Area of Science:

• Pharmacokinetics and Drug Metabolism
• Analytical Chemistry
• Toxicology

Background:

• Chloroquine (CQ) is an antimalarial drug with a complex metabolic profile.
• Understanding CQ metabolism is crucial for therapeutic drug monitoring and overdose management.
• Previous studies have identified several CQ metabolites, but further investigation is warranted.

Purpose of the Study:

• To reinvestigate the metabolism of 7-chloro-4-(4-diethylamino-1-methylbutylamino)quinoline (chloroquine).
• To identify and characterize CQ metabolites in urine samples from patients and volunteers.
• To analyze CQ and its metabolites in cases of chloroquine overdose.

Main Methods:

• Urine samples were collected from individuals receiving single or repeated CQ doses, and from overdose cases.
• Analysis was performed using gas chromatography (GC), thin-layer chromatography (TLC), and gas chromatography/mass spectrometry (GC/MS).
• Identification of unknown metabolites and characterization of artifacts were key objectives.

Main Results:

• Three previously unidentified CQ metabolites were detected in most urine samples, albeit at concentrations below 2% of unchanged CQ.
• In samples where metabolites were undetectable, CQ levels were below the analytical method's limit of detection.
• An artifact from chloroquine-N-oxide was characterized; a previously reported alcohol-functionalized metabolite was not confirmed.

Conclusions:

• The study identified novel CQ metabolites, contributing to a more comprehensive understanding of its metabolic pathways.
• No evidence of dose-dependent formation for the newly identified metabolites was found.
• Analytical methods confirmed an artifact and refuted the presence of a specific literature-reported metabolite.