High-pressure liquid chromatographic determination of ranitidine, a new H2-receptor antagonist, in plasma and urine.
An assay is described for the determination of a new H2-receptor antagonist, ranitidine, and its desmethyl metabolite in human plasma and urine. Alkalinized plasma or urine was extracted with methylene chloride, the organic phase was evaporated, and the reconstituted residue was analyzed by high-pressure liquid chromatography using a reversed-phase column. Two other identified metabolites of ranitidine, the S-oxide and N-oxide, were separated chromtographically from both ranitidine and the desmethyl metabolite. However, these metabolites could not be quantitative due to poor analytical recovery and interference from endogenous components. The sensitivity limits were 5 ng/ml for ranitidine and 15 ng/ml for desmethylranitidine. Plasma samples from two volunteers who were given oral ranitidine (0.1, 0.2, and 0.4 mg/kg) at 1-week intervals were assayed. Peak levels of 30--130 ng/ml were achieved between 40 and 120 min after dosage, followed by an elimination half-life of 2.9-3.9 hr. Plasma levels of ranitidine were still detectable at 8 hr but were below the sensitivity of the assay by 24 hr. Plasma levels of the desmethyl metabolite were seldom above the threshold sensitivity of the assay. Urinary excretion of unmetabolized ranitidine accounted for 77% of the administered dose, whereas only 4% appeared as desmethylranitidine.
D000328:Adult; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D005663:Furans / Q000032:analysis* / Q000097:blood / Q000652:urine; D006801:Humans; D008297:Male; D011899:Ranitidine
D005663:Furans; D011899:Ranitidine