Determination of disulfiram and two of its metabolites in urine by reversed-phase liquid chromatography and spectrophotometric detection after post-column complexation.

A selective method was developed for the determination of disulfiram and two of its metabolites, diethyldithiocarbamate (DTC) and copper (II) diethyldithiocarbamate [Cu(DTC)2], in complex (biological) samples by reversed-phase liquid chromatography (RP-LC) with post-column derivatization. In the first step, DTC is converted into lead (II) diethyldithiocarbamate [Pb (DTC)2] by adding lead (II) acetate. Disulfiram, Pb (DTC)2 and Cu (DTC)2 can be easily pre-concentrated on C18-bonded silica. After separation by isocratic RP-LC, derivation takes place in two solid state post-column reactors packed with metallic copper and copper (II) phosphate. Disulfiram reacts with metallic copper to form Cu (DTC)2. The same product is obtained by the ligand-exchange reaction between Pb (DTC)2 and copper (II) phosphate. Cu (DTC)2 can be detected selectively at 435 nm with good sensitivity (molar absorptivity, epsilon = 13,000). The derivatization reactions proceed rapidly and quantitatively, which was confirmed by comparison of absorption spectra. The applicability of this method is demonstrated for undiluted urine samples which, apart from the addition of lead (II) acetate and pre-concentration of C18-bonded silica, require no clean-up procedure.

[Urinary excretion of diethyldithiocarbamate (DDC) after antabuse administration to workers chronically exposed to carbon disulfide]. / Wydalanie dwuetylodwutiokarbaminianów (DDC) z moczem po podaniu antabusu u pracowników przewlekle narazonych na dwusiarczek wegla.

Djuricz's antabus test has been applied in a group chronically exposed to carbon disulphide. Sixty eight viscose industry workers hospitalized in the Clinic of Occupational Diseases, Institute of Occupational Medicine, Lódz, have been examined along with controls. In all subjects, after oral administration of antabus, the content of diethyldithiocarbamates (DDC) was determined in a 5 hr urine sample. The mean values of excreted DDC have indicated a statistically significant decrease in those chronically CS2 exposed, as compared to the controls. The dependence of DDC excretion on the duration of work in exposure has indicated a clear decrease in the values in those chronically exposed as compared to those exposed for a short time. The obtained results confirm the observations of other authors on DDC excretion decrease in CS2 exposed workers, demonstrating simultaneously some effects of chronic CS2 exposure on antabus metabolism.

[Diagnostic value of antabuse and CBJ-131 test in workers chronically exposed to carbon disulfide]. / Wartosc diagnostyczna testu antabusowego i testu CBJ131 u pracowników przewlekle eksponowanych na dwusiarczek wegla.

The studies covered 32 workers chronically exposed to CS2 and controls. In all subjects diethyldithiocarbamaturia was evaluated and J131 labelled Bengal Rouge decay half-time was determined. The studies indicated statistically significantly lower DDC excretion in CS2 exposed workers, as compared to controls. On the other hand no statistically significant differences were found at the Bengal rouge decay half--time in blood. The above studies suggest that the disulphuran metabolic route was impaired prior to the occurrence of the changes in liver blood flow of CS2 exposed workers.

Determination of disulfiram and metabolites from biological fluids by high-performance liquid chromatography.

A high-performance liquid chromatographic method is described for the determination of disulfiram, diethyldithiocarbamate, diethyldithiocarbamate methyl ester, carbon disulfide, and diethylamine from a single sample of plasma or urine. The analytical procedure is based on a quantitative stepwise extraction of disulfiram and diethyldithiocarbamate methyl ester, or the conversion of diethyldithiocarbamic acid, carbon disulfide and diethylamine to diethyldithiocarbamate methyl ester for chromatographical determination. The procedure is specific, precise and simple. The application of the analytical methods developed for the determination of disulfiram and the various metabolites in plasma from mice given disulfiram intraperitoneally or humans given Antabuse orally is illustrated.

Radioactive and nonradioactive methods for the in vivo determination of disulfiram, diethyldithiocarbamate, and diethyldithiocarbamate-methyl ester.

Although disulfiram (tetraethylthiuram disulfide; DSF) has been used in the treatment of alcoholism for almost a quarter of a century, little is known about its in vivo metabolism. One reason for this is that few analytical methods are available that can determine DSF and its various metabolites in biologic fluids and tissues. This article describes two simple procedures for the determination of these substances.

Methods for detecting disulfiram in biologic fluids: application in studies of compliance and effect of divalent cations on bioavailability.

Studies regarding the efficacy of disulfiram in the treatment of alcoholism have not included a method of evaluating compliance to the prescribed regimen. This article outlines current methods used to detect disulfiram in blood, breath, and urine.