Electrocatalytic evaluation of graphene oxide warped tetragonal t-lanthanum vanadate (GO@LaVO4) nanocomposites for the voltammetric detection of antifungal and antiprotozoal drug (clioquinol).

Metastable and rarely reported GO warped tetragonal phase t-lanthanum vanadate nanocomposites (GO@LaVO4-NCs) are reported for the sensitive electrochemical determination of antifungal drug Clioquinol (CQ). The hydrothermal method was adopted for synthesis of GO@LaVO4-NCs. The electrochemical performance of CQ was examined using cyclic voltammetry (CV) and differential plus voltammetry (DPV) at GO@LaVO4-NCs modified glassy carbon electrode (GCE). The electrocatalytic oxidation of CQ at the GO@LaVO4-NCs/GCE shows the highest anodic peak current at a potential of +0.51 V vs. Ag/AgCl. The proposed sensor provides excellent sensitivity of 4.1894 µA µM-1 cm-2, a very low detection limit (LOD) of 2.44 nM, and a wide range of 25 nM to 438.52 µM towards CQ detection. Finally, the detection of CQ in biological media was successfully done using the GO@LaVO4-NCs/GCE and possesses recoveries of 94.67-98.0%.

Sex difference of the metabolic disposition of clioquinol in rats.

The order of plasma levels of clioquinol and its conjugates in male rats after intraduodenal administration of 32.7 mumol/kg dose of clioquinol was clioquinol sulfate (C-Sul) greater than glucuronide (C-Glu) much greater than clioquinol, whereas that in female rats was C-Glu greater than C-Sul much greater than clioquinol. Total (urine + bile) recovery was almost the same among male and female rats. The percentage of excretion amounts of C-Sul (urine + bile) to the total excretion amounts for 24 h in male rats after intravenous administration of clioquinol was about twice that in female rats, while the percentage of excretion amounts of C-Glu to the total excretion amounts in male rats was smaller than that in female rats. In intravenous administration of 16.4 mumol/kg dose of C-Glu, C-Sul and clioquinol other than C-Glu were found in bile and urine of male and female rats. The percentage of excretion amounts of C-Sul and C-Glu (urine + bile) to the total excretion amounts was similar among male and female rats, respectively. In intravenous administration of 16.4 mumol/kg dose of C-Sul, C-Glu and clioquinol other than C-Sul were found in bile and urine of male and female rats, and the percentage of excretion amounts of C-Sul (urine + bile) to the total excretion amounts in male rats was 1.3 fold that in female rats.(ABSTRACT TRUNCATED AT 250 WORDS)

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

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.

Enterohepatic circulation of clioquinol in the rat.

The existence of the enterohepatic circulation (EHC) of clioquinol was confirmed by using paired rats, donor and recipient, which were connected to each other with a bile duct-to-duodenum cannula. The concentrations of clioquinol and its metabolites appearing in the plasma of the recipient following intraduodenal 10 mg/kg dose of clioquinol to the donor were fairly low. However, within 24 h after the administration ca. 12% of the dose was reexcreted in the bile of the recipient as clioquinol glucuronide and ca. 2% in the urine as clioquinol sulfate. From these results and the data of biliary excretion in our previous paper, the glucuronide was found to play a role on the EHC. Further, both in vitro and in situ results suggested that clioquinol glucuronide excreted in the bile may be absorbed partially after return to the parent drug in the intestinal tract and partially as such without deconjugation.

Metabolism of 14C-iodochlorhydroxyquin in the dog and the rat.

The disposition and metabolism of iodochlorhydroxyquin (clioquinol), an amebicidal drug with neurotoxic properties, were studied in dogs and rats with 14C-labelled drug. Pharmacokinetic studies in the dog demonstrated that the compound was well absorbed; the bioavailability was 36% of the dose of 1 mg/kg. The serum half-life was 1.3-1.8 h. In both the dog and the rat, biliary excretion was a major route of elimination. The dog excreted 27% of an intravenously administered dose (1 mg/kg) in the bile within 2 h; the rat excreted 39% of the dose (5 mg/kg i.v.) in less than 3 h. Elimination via the renal route was also substantial in both species. Urinary and biliary metabolites were separated by TLC (thin layer chromatography) and identified as sulfate and glucuronide conjugates in both species. No evidence for any other metabolites was found. A significant difference was observed between the dog and the rat in the extent of conjugation; the percentage radioactivity in the urine accounted for by the unchanged compound was six to twenty times greater for the dog than for the rat. The species differences in the disposition and metabolism of the compound might explain its greater toxicity in the dog than in the rat.

Analysis of iodochlorhydroxyquin in biological materials by high-performance liquid chromatography.

A reversed-phase high-performance liquid chromatographic system using a mobile phase of 0.05 M phosphoric acid--methanol (30:70) was developed for determination of iodochlorhydroxyquin (clioquinol, I) in biological material. I was extracted from samples with diethyl ether. Conjugates of I were hydrolyzed to free I and extracted by the same method. The ether phases were evaporated to dryness, reconstituted in the mobile phase and chromatographed using a microparticulate C18 column, a pre-column and a UV detector set at 256 nm. Quantitation of I in the range of 0.20-2.0 micrograms/ml of urine, 0.50-2.0 micrograms/g of liver, and 0.25-2.0 micrograms/g of feces was obtained with coefficients of variation of 0.02, 0.05, and 0.06, respectively. The detection limit of I was 0.2 micrograms. Extensive absorption of I upon topical application to dogs was also demonstrated.

Percutaneous absorption of clioquinol (Vioform).

The percutaneous absorption of clioquinol from three different preparations for skin treatment (Vioform cream, Locacorten-Vioform cream and Vioform-Hydrocortisone cream) was evaluated. After topical dosages corresponding to 30 mg clioquinol, concentrations in the blood were below the detection limit of the analytical procedure, i.e., smaller than 0.02 micrograms/ml; therefore the percutaneous absorption was evaluated by measuring cumulative urinary excretion of clioquinol and was compared to that found after an equivalent oral dose. The study was carried out in 4 healthy volunteers. The topical preparations were applied under occlusive dressings. Following epicutaneous application of the three topicals in quantities containing 30 mg clioquinol each, the urinary excretion of the drug was between 1.2 and 3.6% of the applied dose. When the same dose of clioquinol was administered orally to two volunteers, 52.4 and 92.9% of the dose was excreted in the urine. Taking the urinary elimination as the minimal amount of drug absorbed, the extent of percutaneous absorption from the three dermatological preparations amounted to 1.2-3.6% of the applied dose. There was no difference in the pattern of urinary excretion products among the three topicals and the oral formulation. The bulk of clioquinol was excreted as glucuronide (mean: 96 +/- 3%) and only a small fraction was excreted as sulfate (mean: 3.8 +/- 3%). A small amount of free clioquinol (1.1%) was measured in 1 subject only after the oral dose.

The determination of clioquinol in biological materials by extractive alkylation and gas-liquid chromatography.

Clioquinol, or 5-chloro-7-iodo-8-hydroxyquinoline (Vioform), and the internal standard, 5,7-dichloro-8-hydroxyquinoline are extracted from biological material in the form of their tetrahexylammonium salts into dichloromethane, where, in the presence of a methylating agent, both clioquinol and the standard are spontaneously transformed into their O-methyl derivatives. These derivatives can be purified by base-specific extraction and subsequently determined by gas chromatography; concentrations down to 10 ng per sample may be assayed. The method is compared with a previously reported procedure based on the O-acetyl derivatives.