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Biomedical subjects

J Oxford

Publications and source records attributed to J Oxford.

28 records · Page 2Linked to original sources
PubMed1982

Use of high-performance liquid chromatography-mass spectrometry for the study of the metabolism of ranitidine in man.

High-performance liquid chromatography has been used for the qualitative analysis of metabolites and the quantitative analysis of ranitidine in the urine from subjects given oral and intravenous doses of ranitidine. Ranitidine, ranitidine-N-oxide, ranitidine-S-oxide and desmethylranitidine were identified in extracts of the urine obtained by the XAD-methanol procedure. A selected-ion monitoring technique, using [2H3]ranitidine as the internal standard, was used to determine ranitidine. A normal-phase system consisting of methanol-propan-2-ol-5 M ammonium acetate (50:50:1) was used, and because of this the volume of urine which could be injected on-column without deterioration of the chromatography was limited to 10 microliters. This limited the sensitivity of the method to 1.0 microgram of ranitidine per millilitre of urine.

Administration, Oral↗
PubMed1981

The use of on-line high-performance liquid chromatography-mass spectrometry for the identification of ranitidine and its metabolites in urine.

1. Reverse and normal phase h.p.l.c. systems have been developed for separation ranitidine and three metabolites, desmethylranitidine, ranitidine-S-oxide and ranitidine-N-oxide. 2. These h.p.l.c. systems have been evaluated for characterization of ranitidine and metabolites using an h.p.l.c. coupled to a mass spectrometer with a moving belt interface. 3. Ranitidine and its metabolites were thermally degraded under the conditions required to evaporate the reverse phase eluent that contained 40% aq. 0.05 M ammonium acetate. 4. The normal phase eluent was evaporated in the interface at a lower temp. and satisfactory mass spectra were obtained from 1 microgram of ranitidine and each metabolite injected on to the h.p.l.c. column. 5. Normal phase h.p.l.c.-mass spectrometry has been used to identify ranitidine and three of its metabolites in rabbit and human urine obtained after oral administration of ranitidine.

Animals↗
PubMed1979

The determination of terbutaline in human plasma by selected ion monitoring of the t-butyldimethylsilyl ether.

A method is described for the quantitative determination of terbutaline in 2 ml human plasma. The drug is extracted from plasma as the terbutaline tetraphenylboron ion pair and determined by gas chromatography mass spectrometry of its t-butyldimethylsily ether. Salbutamol is used as internal standard. Quantification is achieved by selected ion monitoring of the ion m/z 482 derived from t-butyldimethylsilyl terbutaline and m/z 495 from t-butyldimethylsilyl salbutamol. The detection limit was estimated to be 250 pg terbutaline ml-1 plasma. The coefficient of variation at the level of 1 ng terbutaline ml-1 was 4.1% (n = 5).

Albuterol↗
PubMedDate not supplied

Disposition of sumatriptan in laboratory animals and humans.

Sumatriptan is a new 5HT1-like agonist that has proved a novel and effective treatment for migraine. The disposition of the 14C-radiolabeled drug in laboratory animals and humans after oral and parenteral administration is described. Oral absorption of sumatriptan is essentially complete in dogs and rabbits, but only approximately 50% in rat. In humans, at least 57% of an oral dose is absorbed. Bioavailabilities are species dependent (14, 23, 37, and 58% in humans, rabbits, rats, and dogs) reflecting differing degrees of first-pass metabolism. These data correlate well with hepatic extraction ratios, which are highest in rabbits and humans and lowest in dogs. Renal clearance is significant in all species and exceeds the glomerular filtration rate in rats, rabbits, and humans, but not in dogs. The compound is a weak base that shows widespread tissue distribution, including passage across the placental barrier and into milk, but low CNS penetration. Protein binding of sumatriptan is low in all species. Elimination half-lives of sumatriptan are approximately 1 hr in rats and rabbits, and approximately 2 hr in dogs and humans. In all species the majority of the absorbed dose is renally excreted, predominantly as the indole acetic acid metabolite and unchanged drug. Interesting species differences are evident in the metabolism of sumatriptan. Thus, in humans, the indole acetic acid metabolite is excreted partly as a glucuronide, whereas in animals conjugation of this metabolite is not apparent. In addition, demethylation of the sulfonamide side chain of the drug is evident in rodent and lagomorph species only.

Administration, Oral↗
PubMedDate not supplied

Disposition of salmeterol xinafoate in laboratory animals and humans.

The disposition of [14C]salmeterol xinafoate, a new inhaled beta 2-adrenoceptor agonist with both bronchodilator and antiinflammatory activity, has been studied in laboratory animals and humans following intravenous and oral administration. [14C]Salmeterol was rapidly absorbed in animal species and humans with Cmax observed within 2 hr. Cmax was similar for normalized oral dose level in mice, rats, and rabbits. In dogs, Cmax was higher and reflected the greater oral bioavailability in this species. The plasma t1/2, after intravenous administration, was 5 hr in rats and 2 hr in dogs. The volume of distribution of salmeterol was significantly greater than total body water in both rats (40 liters/kg) and dogs (6 liters/kg) and indicated high tissue uptake of the compound. Plasma clearance was high in rats (95 ml/min/kg) and dogs (30 ml/min/kg). Radioactive drug-related material was widely distributed throughout body tissues in rats. The highest concentrations were present in kidney, liver, gastrointestinal tract, pituitary, lung, heart, and bone marrow. Transfer of radioactive drug-related material across the placental barrier or into milk, studied in rats, was low. In all species the majority of an oral or intravenous dose (55-75%) was excreted in feces. Biliary excretion in rats and dogs accounted for 53% (0-27 hr) and 40% (0-8 hr) of an oral dose, respectively, indicating good absorption across the gastrointestinal tract. Enterohepatic circulation was significant in rats. Salmeterol was cleared predominantly by metabolism in animals and humans.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗