A. H. Beckett

Routine detection and identification in urine of stimulants and other drugs, some of which may be used to modify performance in sport

A general procedure for the analysis in urine of basic drugs (and their metabolites), some of which may be misused as stimulants in sport, has been developed. The techniques used include gas‐liquid and thin‐layer chromatography and linked gas‐liquid chromatography—mass spectroscopy. It is recommended that international control of drug‐taking in sport be based primarily upon urine analysis by gas‐liquid chromatography systems and also derivative formation followed by gas‐liquid chromatography. The principles outlined in the procedure can be applied in a much wider forensic context.

Urinary excretion kinetics of amphetamine in man

The urinary excretion of amphetamine has been examined in 11 male subjects after oral administration of (+)‐ and (–)‐ amphetamine sulphate. The excretion of unchanged drug was shown to be dependent upon urinary pH. Excretion of amphetamine, when the urine was maintained alkaline or acid, was measured in seven subjects. The implications of these results, especially in the evaluation of dosage forms, are discussed.

The biotransformation of methadone in man: Synthesis and identification of a major metabolite

After administration of methadone to man, only two basic urinary excretion products were detected, these were unchanged drug and 2‐ethyl‐1, 5‐dimethyl‐3, 3‐diphenyl‐1‐pyrroline. The hydriodide of the latter was synthesized and its endocyclic alkene structure was confirmed from infrared and nuclear magnetic resonance spectral data. This compound was shown to be identical with the hydriodide of the basic product formed by reaction of 1, 5‐dimethyl‐3, 3‐diphenylpyrrolid‐2‐one with ethyl‐lithium.

Urinary excretion kinetics of methylamphetamine in man

The urinary excretion of methylamphetamine and its metabolite, amphetamine, was studied after oral administration of (+)‐ and (–)‐methylamphetamine hydrochloride to three male subjects. Fluctuations in the excretion rate of both amines occurred and were associated with changes in urinary pH. The fluctuations were abolished when the urine was maintained either acid or alkaline, by administration of ammonium chloride and sodium bicarbonate respectively. The total amount of both amines excreted was lower under alkaline than acid urine conditions. N‐Demethylation of methylamphetamine was small, but greater for the (+)‐ than the (–)‐isomer.

Substituted oxindole—I : The preparation and spectral characteristics of some simple oxindole derivatives

Abstract A series of oxindole derivatives substituted in the aromatic ring and their N-Me homologues has been prepared. The effects of position and nature of substituents on the IR, NMR and UV spectra have been investigated. Evidence is presented which indicates the presence of an intermolecular hydrogen bond in solutions of oxindole and certain N-unsubstituted derivatives. A relationship between Hammetts σ constant of substituents and the carbonyl frequencies of these oxindoles is reported.

The relation between blood levels and urinary excretion of amphetamine under controlled acidic and under fluctuating urinary pH values using [14C]amphetamine

Plasma, blood cell and urine levels of amphetamine were determined after the oral administration of S‐(+)‐[14C]amphetamine sulphate to two subjects under conditions of controlled acidic and fluctuating urinary pH. The decline in plasma concentration of the drug was more rapid under the controlled acidic conditions than under conditions of fluctuating urinary pH. Under controlled conditions, the concentration time profiles of drug and metabolite in urine or plasma (as opposed to body levels), were suitable for kinetic analysis. The apparent rate of urinary excretion of amphetamine was proportional to its plasma concentration only under the controlled acidic urinary conditions. Amphetamine was cleared from blood more rapidly than could be accounted for by glomerular filtration under acid conditions, but when urinary pH fluctuated, clearance of the drug could be accounted for by this route.

THE IMPORTANCE OF STEREOISOMERISM IN MUSCARINIC ACTIVITY

The muscarinic activities and rates of hydrolysis by acetylcholinesterase of the optical isomers of the acetyl‐α‐ and acetyl‐β‐methylcholines of known configuration have been determined. The results have been correlated and the possible characteristics of muscarinic receptors outlined.

SURFACE‐ACTIVE BETAINES: N‐ALKYL‐NN‐DIMETHYLGLYCINES AND THEIR CRITICAL MICELLE CONCENTRATIONS

A series of surface‐active N‐alkyl NN‐dimethyl glycines (alkyl betaines) and their hydrochlorides have been prepared. Some physical properties of these compounds have been investigated. The critical micelle concentrations of the betaines have been determined by a surface tension, a refractive index, a dye solubilisation and an iodine method. An explanation of the differences in critical micelle concentrations between these amphoteric surfactants and corresponding anionic and cationic surfactants is proposed.

Metabolism of chlorpromazine in humans

Abstract The isolation and characterisation of chlorpromazine metabolites from the urine of psychiatric patients is described. It is shown that chlorpromazine and its mono-and di-demethlated derivatives are hydroxylated and that these hydroxy compounds are conjugated mainly with glucuronic acid and, to a lesser extent, with sulphate. The predominant metabolite was isolated and identified as a monoglucuronide of N-desdimethyl chlorpromazine.

Corynantheidine-type alkaloids—I : Establishment of physical criteria for the normal, pseudo, allo and epiallo configurations by conformational analysis

Abstract Corynantheidine-type alkaloids have three asymmetric centres (C3, C15, C20); the four possible configurations (each an enantiomorphic pair) can each exist in three ring D chair conformations. The twelve possible chair conformations are subjected to conformational analysis to try to determine the preferred conformation(s) of each configuration. The analysis demonstrates one preferred conformation for each configuration which allows the assignment of distinguishable physical properties (IR, NMR, ORD, CD) for the eight stereoisomers. Application of these physical criteria allows assignment of absolute configuration to ring substituted or unsubstituted corynantheidine-type alkaloids of unknown configuration.