A specific method for the determination of amphetamine in urine

Beckett, A. H.; Rowland, M.

doi:10.1111/j.2042-7158.1964.tb07535.x

Cited by 19 publications

(5 citation statements)

References 8 publications

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“…The model used in this study is the one that has been developed by Hansch and his co-workers (1) and used extensively in a number of different biological applications (1)(2)(3)(4)(5). In effect, the model assumes that the amount of drug found a t the receptor site is related to a single substituent constant which is derived from octanol-water partition-coefficient measurements.…”

Section: Tructure-activity Relationships Have Beenmentioning

confidence: 99%

Fenfluramine Metabolism

Bruce

Maynard

1968

Journal of Pharmaceutical Sciences

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The metabolism of fenfluramine in man results in the excretion of unchanged fenfluramine, deethylated fenfluramine, and m-trifluoromethylhippuric acid. Methods are described for the determinations of these three compounds and the total metabolites in urine by GLC. The m-trifluoromethylhippuric acid accounts for 66 to 9 3 percent of the dose and 79 to 100 percent of the dose may be accounted for as these three metabolites.phenethylamine hydrochloride] is an effective anorexigenic agent showing little or no CNS stimulant properties (1). Structurally, this compound is similar to the amphetamines.Duhault and Fenard (2) have reported a study of the excretion, distribution, and metabolism of fenfluramine using methyl orange complex for its determination. They found that fenfluramine persists in the animal body for considerably longer than amphetamine. The total excretion following oral doses in man and in dogs was 2 i to 380/, of the dose over a 5-to 6-day period.Relatively large amounts were found in fatty tissues of the dog. These authors found that the drug is deethylated but could find little or no evidence for hydroxylation, as occurs with amphetamine. Beckett and Brookes (3), using gas chromatographic methods, have studied the dependence of the rate of excretion on urinary pH. They found that some 50% of feduramine was excreted unchanged or deethylated under acidic urinary conditions, but could account for only 6 to 23y0 with uncontrolled acidity of the urine. The relatively low recoveries of the amines, which has been confirmed in these laboratories, led the authors to investigate the fate of the remainder of the drug in the animal body. Extensive use of gas chromatography in these studies was made to determine the amounts of unchanged drug and its metabolities in biological materials. Blood levels in man and the dog have been determined by GLC. The results given below indicate that the major portion of an oral dose of fenfluramine in man is excreted as m-trifluoromethylhippuric acid (Scheme I). EXPERIMENTAL.Human Study-Two normal, healthy males were given a 60-mg. tablet of fenfluramine as a single dose, and urine was collected at intervals for 72 hr. Ammonium chloride was administered the previous day and throughout the period of urine collection, . tories, A. H. Robins Company, Inc.. Richmond, V A 23220 in an attempt to maintain an acidic urine. All urine samples were kept in the refrigerator until analysis. The pH of each sample was determined with a pH meter immediately upon receipt. Blood samples of 20 ml. were collected at intervals during the first 8 hr. for analysis.Dog Study-A mongrel male dog weighing 11.7 kg. was given a divided oral dose of 117 mg. of fenfluramine, and urine was collected for 5 days and stored under refrigeration.Materials-rn-Trifluoromethylbenzoic acid was purchased from J. T. Baker Chemical Co. m-Trifluoromethylhippuric acid was prepared by reaction of m-trifluoromethylbenzoic acid with thionyl chloride to give m-trifluoromethylbenzoyl chloride. The acid chloride was then reacted ...

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Section: Tructure-activity Relationships Have Beenmentioning

confidence: 99%

Fenfluramine Metabolism

Bruce

Maynard

1968

Journal of Pharmaceutical Sciences

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“…Amphetamine, in urine, was determined by the gas-liquid chromatographic method described by Beckett & Rowland (1965a). Some of the results were obtained by the method of Beckett & Rowland (1964b). In some instances amphetamine was further identified as its acetone derivative (Beckett & Rowland, 1965a).…”

Section: Determination Of Amphetaminementioning

confidence: 99%

Urinary excretion kinetics of amphetamine in man

Beckett¹,

Rowland²

1965

Journal of Pharmacy and Pharmacology

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201

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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.

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“…The total time necessary for the analysis of sixteen samples is about 6 hr, which is shorter than that for the previous method (Beckett & Rowland, 1964). Furthermore less sample is required and assays of 0.1 pg amphetamine base per ml urine may be made without interference from constituents in urine.…”

Section: Determination and Identification Of Amphetamine In Urinementioning

confidence: 94%

“…SrR,-We report herein an improved and more convenient method than that reported previously, for the determination and identification of amphetamine in urine (cf. Beckett & Rowland, 1964). The determination is based on a niodification of the method of Cartoni & Stefan0 (1963).…”

Section: Determination and Identification Of Amphetamine In Urinementioning

confidence: 99%