Effect of oxygen-carrying resuscitation fluids on the pharmacokinetics of antipyrine, diazepam, penicillin, and sulfamethazine in rats.

The effects of exchange transfusion with an oxygen-carrying resuscitation fluid, Fluosol DA 20% or stroma-free hemoglobin, on the pharmacokinetics of antipyrine, diazepam, penicillin, and sulfamethazine were studied in rats. After transfusion with Fluosol DA 20% or stroma-free hemoglobin the pharmacokinetics of antipyrine, diazepam, and penicillin were unchanged when compared to control animals. After transfusion with Fluosol DA 20%, the t 1/2 of sulfamethazine was increased from 3.

Human metabolism of tolfenamic acid. II. Structure of metabolites and C-13 NMR assignments of fenamates.

Metabolites of tolfenamic acid appearing in human urine have been isolated and their structures determined by C-13 nuclear magnetic resonance and gas chromatography-mass spectrometry. Comparative studies on tolfenamic, mefenamic, and flufenamic acids in conjunction with the metabolites have permitted complete C-13 NMR assignments for this series of compounds. Five metabolites identified included three that were monohydroxylated, one that was both methoxylated and hydroxylated, and another in which the methyl group was oxidized to a carboxyl group.

Formation of methyl ester of salicyluric acid during quantitation of salicyluric acid in urine by high-pressure liquid chromatography.

The formation of the methyl ester of salicyluric acid was observed during the quantitation of salicyluric acid and other salicylate metabolites in urine by high-pressure liquid chromatography. This methyl ester formation caused artificially low values for salicyluric acid and high values for salicylic acid.

Evidence for the stimulation of dolichol and mannolipid synthesis by glucocorticoids in HeLa cells.

The effects of addition of 1 microM-dexamethasone on the rate of transfer of mannose from GDP-mannose into mannolipid have been studied in HeLa cell cultures. Concurrent with an increase in incorporation of mannose into glycoproteins, the incorporation of mannose from GDP-mannose in vitro into mannolipid and dolichol-linked oligosaccharides was increased after dexamethasone treatment. Stimulation of mannolipid synthesis showed a correlation with the 11 beta, 17 alpha, 21-trihydroxy structure of C21 steroids.

Kinetics of R andS warfarin enantiomers.

A method is reported for simultaneous measurement of the kinetics of R and S warfarin enantiomers. Pure pentadeuterated R and S enantiomers were each combined with unlabeled enatiomers to form "pseudo"-racemic mixtures which were given (0.75 mg/kg) to 5 healthy subjects.

Topical application of lindane cream (Kwell) and antipyrine metabolism.

The transcutaneous absorption of a 1% lindane cream (Kwell) was determined after application according to the official label. By 3 days after application the plasma lindane level increased from nondetectable to 10.3 +/- 2.

Quantitation of lidocaine and its deethylated metabolites in plasma and urine by gas chromatography-mass fragmentography.

A sensitive, precise and accurate method for simultaneous quantitation of lidocaine and its deethylated metabolites by gas chromatography-mass fragmentography has been developed. Propyl derivatives of the deethylated metabolites are formed directly in either plasma or urine by treatment with propionaldehyde and sodium cyanoborohydride. The propyl derivatives and unchanged lidocaine are extracted, separated by gas chromatography and quantitated by mass fragmentography using mepivacaine as the internal standard.

Quantitation of N-demethylantipyrine in biological samples and isolation and characterization of its glucuronic acid conjugate.

An improved method for quantitating N-demethylantipyrine (N-DEM-AP) in urine by gas chromatography or gas chromatography-mass spectrometry has been developed. Recovery of greater than 90% of N-DEM-AP was achieved by extraction of the sample at pH 1 after addition of 3-amino-1-phenyl-2-pyrazolin-5-one. The coefficient of variation of replicate analyses was 8%.

Correlation between plasma diphenhydramine level and sedative and antihistamine effects.

The sedative and antihistamine effects of diphenhydramine were assessed in relation to plasma concentration after placebo, diphenhydramine 50 mg intravenously, and diphenhydramine 50 mg orally to each of 6 healthy volunteers on three separate occasions. Diphenhydramine plasma elimination t1/2 was 3.0 to 4.

Identification of methotrexate and folic acid analogs by mass spectrometry.

Methotrexate and folic acid analogs are polar molecules and attempts to obtain electron impact and chemical ionization mass spectra of these compounds by several laboratories have failed. We have found that methylation of this important class of compounds with diazomethane produces derivatives which are sufficiently volatile to allow their mass spectra to be recorded. The mass spectra of the methyl derivatives of five compounds, 4-amino-4-deoxy-N10-methylpteroylglutamic acid, 4-amimo-4-deoxypteroylglutamic acid, pteroylglutamic acid, 4-amino-4-deoxypteroic acid and N10-methylpteroylglutamic acid are presented, and the fragmentation pathways of these compounds discussed.

Separation and identification of impurities in parenteral methotrexate dosage forms.

Eleven lots of parenteral methotrexate (MTX) dosage forms from two manufactures have been analyzed and found to be 93.4% +/- 2.1% (SD) pure by a new procedure employing a DEAE-cellulose column adapted for high performance liquid chromatography instrumentation.

Metabolic disposition of antipyrine in patients with lung cancer.

The metabolism of antipyrine (10 mg/kg i.v.) was studied in nine patients with cancer of the lung and in a cancer-free control group matched for age, sex, drug intake, and smoking and drinking history.

Serum quinidine concentrations: comparison of fluorescence, gas-chromatographic, and gas-chromatographic/mass-spectrometric methods.

Serum quinidine concentrations were determined in patients on chronic therapeutic doses. Although results were higher by a protein precipitate-fluorescence method as compared to a specific extraction fluorescence method, there was substantial correlation between results by the two methods (r = 0.945, P less than 0.

In vitro inhibition of rat liver cholest-5en-3 beta-ol (cholesterol) biosynthesis by non-mercurial sulfhydryl reagents.

In vitro conversion of 2-14C-mevalonate to cholest-5en-3 beta-ol (cholesterol) in rat liver homogenates is inhibited by arsenite, beta-mercaptoethanol, dithiothreitol and ethanethiol. Two sterols containing 20 carbon atoms accumulate under these conditions. One of these is identified as 4,4 dimethyl-5alpha-cholest-8en-3beta-ol and the other tentatively identified as 4,4 dimethyl-5alpha-cholest-8,24-dien-3beta-ol.