The Detection and Determination of Drugs and Their Metabolites in Biological Fluids

Thorpe, James W (1972) The Detection and Determination of Drugs and Their Metabolites in Biological Fluids. PhD thesis, University of Glasgow.

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This thesis is concerned with the detection, identification and estimation of drugs and their metabolites in body fluids. The principal drugs studied were the halogenated drugs chlorbutanol and chloral hydrate. One widely used technique for the detection of chloral hydrate and its metabolite, trichloroacetic acid, is the Fujiwara test. This test was also known to be capable of detecting chlorbutanol. The reaction conditions were studied to determine the optimum conditions for the detection of chlorbutanol. As part of the investigation into the optimum conditions an investigation was carried out into the mechanism of the Fujiwara reaction. Previously this test was thought to detect only a series of halogenated compounds. This investigation showed, however, that this is not correct. A positive reaction can be obtained if the reaction conditions lead to the attachment of an electrophilic group to the nitrogen atom of a pyridine ring if this group, in the presence of base, gives rise to a conjugated system which can give rise to an ionised species. A modification of this test was also used for quantitative estimation of the metabolites of chloral hydrate. For the identification of the drugs in body fluids gas chromatography was found to be the most suitable technique. A number of possible systems were investigated and the most suitable chosen for the routine identification and estimation of these drugs. This technique was preferred to the Fujiwara test for estimations as more than one drug can be readily estimated in the same sample. The Fujiwara test was used to study the excretion of chlorbutanol by racing greyhounds, in conjunction with a comprehensive study designed to assess all aspects of the drug's effects on these animals. A similar study was carried out using phenobarbitone. The gas chromatographic technique was used to investigate the effectiveness of the Fujiwara technique developed, and also a number of aspects relating to the handling of samples thought to contain chlorbutanol. Both the Fujiwara and gas chromatographic techniques were employed in the routine analysis of samples. A study was also carried out into the rapid detection of phenylbutazone and contraceptive steroids. Existing techniques were found to be satisfactory for the detection of phenylbutazone and its metabolites, and these substances were characterised using these techniques. However a simple, speedy technique is not practical for the detection of contraceptive steroids in urine samples. The technique of gas chromatography was also used to identify and estimate a number of volatile materials. This was originally carried out to detect contaminants in the reagents used for the Fujiwara test, but also found an application in a post-mortem analysis. One of the column packings found to be unsuitable for the identification of chlorbutanol was found to be capable of separating a wide range of volatile materials. This range included ethanol and trials were carried out in conjunction with a test of the effect of orally administered fructose upon ethanol metabolism. This column packing was found to be a useful supplement to the standard packing used for the determination of blood and urine ethanol concentrations.

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Keywords: Analytical chemistry, Forensic anthropology
Date of Award: 1972
Depositing User: Enlighten Team
Unique ID: glathesis:1972-78605
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 28 Feb 2020 12:09
Last Modified: 28 Feb 2020 12:09

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