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A semiautomated spectrophotofluorometric method for the determination of trimethoprim in blood, urine, and tissue is described. The initial extraction procedures are performed manually. The subsequent alkaline permanganate oxidation and the chloroform extraction of the fluorescent trimethoxybenzoic acid are performed by the automated system at a rate of 30 specimens/hr. The fluorescence is measured by a microflow cell in a spectrophotofluorometer. The method exhibits the same specificity and precision as the manual procedure, with a sensitivity limit in blood of 0.2 mcg./ml.

Clonazepam appears to be well absorbed, exhibiting peak blood levels of 6.5–13.5 ng/ml at 1–2hr after administration in human subjects receiving 2-mg single oral doses. The “apparent” half-lives of elimination ranged from 18.7 to 39hr in the subjects studied. Less than 0.5% of the dose is recoverable in the urine, suggesting complete biotransformation and/or alternative routes of excretion. Flunitrazepam in the dog is rapidly eliminated and exhibits a “first-pass” metabolism effect following oral administration, whereby the N-desmethyl metabolite is the major detectable drug component in the blood. Neither the drug nor its N-desmethyl metabolite is detected in the urine, suggesting extensive and complete biotransformation.

A six-compartment open-system model is presented to elucidate the physiological disposition of chlordiazepoxide and its two pharmacologically active biotransformation products, Ro 5-0883/1 and Ro 5-2092, in the dog following the intravenous administration of 10 mg./kg. chlordiazepoxide · HCl. The pharmaco-kinetic parameters used in the model were obtained by administering each of the three compounds separately. Excellent agreement was obtained between the plasma levels of intact drug, Ro 5-0883/1, and Ro 5-2092 found after administration of chlordiazepoxide · HCl and the calculated levels of each generated from the model. The main features of chlordiazepoxide disposition were: (a) its complete biotransformation to Ro 5-0883/1; (b) elimination of Ro 5-0883/1 almost entirely by biotransformation with up to 50% proceeding to Ro 5-2092 by oxidative deamination; and (c) elimination of Ro 5-2092 by urinary excretion and further biotransformation.