Determination of chinoform in biological fluids and nervous tissues of the dog by gas chromatography-mass spectrometry

Abstract

A sensitive gas chromatographic-mass spectrometric method for the determination of 5-chloro-7-iodo-8-hydroxyquinoline (chinoform, clioquinol) in biological fluids and nervous tissues is described. Chinoform was converted into the pentafluorobenzyl ether, which was separated on a 10% Dexsil 300GC column and determined by the use of chinoform-d4 as an internal standard. The clean-up of chionoform in plasma and urine was efficiently achieved by extracting with benzene, while the drug in the tissue was pretreated successively by extraction with 12.5% v/v pyridine-benzene, separation on a Clin-Elut cartridge and adsorption on alumina. The quantitation limit of chinoform was 100 pg, and the recovery rates of chinoform added to plasma and tissue were 98% and 92%, respectively. The chinoform levels in biological fluids and tissues in dogs after prolonged administration of the drug at a dose of 400 mg/kg/day were measured by the proposed method. The plasma level and tissue distribution of chinoform are also discussed.

Clioquinol: Review of its Mechanisms of Action and Clinical Uses in Neurodegenerative Disorders

“…A subsequent highly sensitive gaschromatographic‐massspectrometric (GC‐MS) method was developed using benzene extraction and the conversion of clioquinol into pentafluorobenzyl ether [14].…”

“…Clioquinol is much less metabolized to form conjugates in humans than in rodents [13,14]. Dose/concentration ratios in hamster are similar to those found in other rodents, but much lower than those found in humans: at doses of 250 or 500 mg the dose/concentration ratio in humans is 0.64–1.4 [12,20], which means that humans have a mean of 33 times the concentrations of free clioquinol found in hamsters.…”

Cu2+-mediated fluorescence switching of gold nanoclusters for the selective detection of clioquinol

“…Recently, particular interest has been devoted to CQ's pharmacodynamics, since CQ is recognized as a potential pharmaceutical against human prostate cancer 6 and neurodegenerative diseases, including Alzheimer's, 7,8 Parkinson's 9 and Huntington's diseases. 10 To date, assays for CQ detection, including thin-layer chromatography, high performance liquid chromatography and gas chromatography-mass spectrometry, [11][12][13] have been developed. However, these methods usually require complex operation and time-consuming derivation processes.…”

Determination of 5-chloro-7-iodo-8-quinolinol (clioquinol) in plasma and tissues of hamsters by high-performance liquid chromatography and electrochemical detection

“…The sensitivity of the GC-MS method of Matsuki et al [20] has a sensitivity of 0.10 ng as the minimum amount injected into the chromatograph which is similar to that of the present method (0.15 ng) but requires a rather complex sample preparation procedure and expensive instruments that are not available in all laboratories.…”

“…An even more complex GC method with electron-capture detection after acetylation has been developed by Jack and Riess [19], which also used solvent extraction with a sensitivity of 50 ng/ml. Finally, a highly sensitive GC-MS method has been developed that uses benzene extraction and the conversion of clioquinol into pentafluorobenzyl ether [20].…”