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Biomedical subjects

L A Sternson

Publications and source records attributed to L A Sternson.

At least 73 records · Page 4Linked to original sources
PubMed1977

Gas chromatographic analysis of acetophenone oxime and its metabolites.

A gas-liquid chromatographic (GLC) method has been developed for monitoring the metabolic reduction of acetophenone oxime or oxidative metabolism of the corresponding amine, alpha-methylbenzylamine in liver homogenates. The oxime, amine, n-hydroxy-alpha-methylbenzylamine and acetophenone are quantitatively determined after GLC separation of components with temperature programming on an SP-2401-DB-coated column. The first three compounds were silylated with N,O-bis(trimethylsilyl)-acetamide prior to chromatographic analysis to enhance the stability and improve the chromatographic properties of these components. The effluent gas was monitored with flame ionization detection, and permitted quantitation of components at sub-microgram/ml levels with reproducibility between injections of +/-2%. The optimal composition of enantiomeric mixtures of (R,S)-alpha-methylbenzylamines formed during metabolic reduction of acetophenone oximes were determined by conversion to diastereomeric amides and subsequent GLC analysis.

Acetophenones↗
PubMed1977

High-pressure liquid chromatographic analysis of aniline and its metabolites.

A high-pressure liquid chromatographic method has been developed for the determination of nanomole quantities of aniline; its metabolites o- and p-aminophenol, phenylhydroxylamine, nitrosobenzene and nitrobenzene; and azobenzene and azoxybenzene which form non-enzymatically by condensation of reactive metabolites. These compounds were separated by reverse-phase chromatography (mu-Bondapak C18 column) and detected spectrophotometrically. The first four components were eluted using methanol-water (15:85) containing 0.26 M ammonium acetate and 0.015 M nickel acetate as mobile phase. The remaining compounds were eluted with methanol-water (50:50). The stabilities of the metabolites were studied electrochemically and results were used in the development of the chromatographic system.

Aniline Compounds↗
PubMed1977

High-performance liquid chromatographic analysis of dianhydrogalactitol in plasma by derivatization with sodium diethyldithiocarbamate.

A high-performance liquid chromatographic method is described for measuring submicrogram quantities of dianhydrogalactitol, a promising anti-neoplastic agent, in plasma. The drug is derivatized directly in plasma with sodium diethyldithiocarbamate to form a bis(dithiocarbamoyl) ester which absorbs UV light at 254 nm (am 17,000). The derivatized product is then extracted quantitatively into chloroform and separated by normal phase chromatography (muBondpak CN column). Dianhydrogalactitol concentration below 50 ng/ml of plasma can be detected in the eluent.

Chemical Phenomena↗
PubMed1977

A preliminary Pharmacokinetic study of dianhydrogalactitol (NSC-132313) disposition in the dog.

The pharmacokinetics of dianhydrogalactitol (DAG), NSC-132313, were studied in the beagle dog at doses of 3 mg - kg-1 and 6 mg - kg-1. DAG concentrations in plasma were determined by a gas chromatographic method capable of specifically detecting the parent drug and differentiating between it and products of its degradation or metabolism. Plasma disappearance time curves were generated and shown to follow simple two-compartment model behavior after iv administration of DAG. Distribution and elimination of DAG appeared to be dose-independent in the limited dose range studied. After iv administration, the drug was rapidly distributed throughout extracellular fluids (volume of the central compartment = 462 ml - kg-1) and subsequently was rapidly cleared (total body clearance = 23.4 ml - min-1 - kg-1) and eliminated (t1/2, b = 26.2 min) from the animal. Experiments (in vitro) with the use of radiolabeled DAG indicated that the drug binds reversibly and irreversibly to red blood cells.

Animals↗
PubMed1977

Measurement of free-circulating cis-dichlorodiammineplatinum(II) in plasma.

Dichlorodiammineplatinum(II) is an anti-neoplastic agent that is currently undergoing clinical evaluation. We describe an analytical method for monitoring the free drug (or its breakdown products) in plasma. The method is able to distinguish between free and protein-bound drug. Plasma samples are deproteinized by centrifugal ultrafiltration. The platinum in the ultrafiltrate is converted to a cationic species by reaction with ethylenediamine and then collected on paper impregnated with cation-exchange resin. This process concentrates the samples, increases the stability of the platinum compounds (by removing the compound from solution), and places the sample in a uniform matrix of minimum thickness, which maximizes detection capabilities. Platinum was measured directly on the ion-exchange disks by X-ray fluorescence. The detection limit for free drug is 240 microgram/liter of plasma at the 3s level and fluorescence intensity is linearly related to drug concentration in the range from 570 to 5700 microgram/liter.

Chromatography, Ion Exchange↗
PubMed1976

Interaction of dantrolene sodium with human serum albumin.

The binding of dantrolene sodium to human serum albumin was studied by fluorescence quenching and difference spectrophotometry. The association constant was calculated from each method of measurement and was large. This binding affinity may be of importance in the clinical setting, since competitive displacement of anionic drug by concurrently administered agents can occur. Consequently, the displacement of dantrolene from albumin was examined with a wide range of drugs. To gain insight into the characteristics of drug-albumin binding, the interaction of drug with cationic, anionic, and nonionic surfactants was also studied. Additions of drug to solutions of either the anionic or nonionic surfactant failed to result in a perturbation with the difference spectral technique. However, dantrolene added to the cationic resin produced a difference spectrum analogous to that observed with the drug-protein interaction.

Dantrolene↗
PubMed1976

Effect of aromatic nitro compounds on oxidative metabolism by cytochrome P-450 dependent enzymes.

The effect of aromatic nitro compounds on the oxidative metabolism of representative type I (hexobarbital and aminopyrene) and type II (aniline and zoxazolamine) substrates by cytochrome P-450 dependent liver enzymes was studied. Nitro compounds (nitrobenzene, p-nitrobenzoate, 2-nitrofluorene, and 2-nitronaphthalene) inhibited the oxidation of type II substrates by rabbit liver microsomal enzymes; however, they had no effect on the metabolism of the type I compounds. Inhibition of type II metabolism was characterized graphically as S,I-hyperbolic non-competitive. The influence of aromatic nitro compounds on the interaction of type I and type II substrates with oxidized and reduced cytochrome P-450 was studied by difference spectroscopy. From Lineweaver-Burke plots, nitro compounds were shown to competitively interact with type II compounds for cytochrome p-450 binding sites. Nitro compounds completely prevented the appearance of a type I binding spectrum with either hexobarbital or aminopyrene even when the modifier was present at concentrations less than 10(-8)M. Aromatic nitro compounds appear to therefore inhibit the metabolism of the type II substrates through a mixed mechanism of interaction with the microsomal drug-metabolizing enzymes.

Aminopyrine↗
PubMed1976

Gas-chromatographic analysis for 1,2:5,6-dianhydrogalactitol, an anti-neoplastic agent, in plasma.

We describe a gas chromatographic method for measuring submicrogram quantities of dianhydrogalactitol, a promising antineoplastic agent (currently undergoing clinical trials in humans), in plasma. The drug is first extracted from blood plasma by saturating the aqueous phase with solid potassium carbonate and extracting with isopropanol/chloroform (9/1 by vol). It is then converted to the corresponding n-butaneboronic ester by reaction at room temperature with butaneboronic acid and chromatographed on an SE-30 (3%) column, with flame ionization detection. Practicality of the method for monitoring drug distribution was demonstrated by administering dianhydrogalactitol in therapeutic doses to a dog and monitoring its concentrations in blood for the next 2 h.

Animals↗
PubMed1975

Species variations in the metabolism of acetophenone oxime by hepatic enzymes.

The metabolism of acetophenone oxime was investigated in liver homogenates obtained from rats, rabbits, mice and hamsters. Significant species variations were observed in anaerobic metabolism studies both in qualitative and quantitative respects. In all cases, the oxime was initially reduced to the corresponding hydroxylamine. Whereas, the hydroxylamine was resistant to further transformation in rat, subsequent reduction to amine was observed in rabbit, mouse and hamster. Hydroxylamine reduction in rat was however observed in animals pretreated with phenobarbital, 3-methylcholanthrene or carbon tetrachloride. Enzymes catalyzing oxime and hydroxylamine reduction were present in both microsomal and cytosol fractions of liver. Highest reductase activity was observed in rat and mouse. Oxime reductase was not stimulated by either phenobarbital or 3-methylcholanthrene, but was inhibited by carbon tetrachloride.

Acetophenones↗