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A high-performance liquid chromatographic procedure was developed for the determination of isophenindamine in phenindamine tartrate bulk powder. The method employs a reversed-phase column and a mobile phase containing methanol, 0.001 M HNO3, and silver nitrate.

We have developed a radioimmunoassay for aprindine, a new antiarrhythmic drug used in the treatment of ventricular disorders. The antibodies were produced by immunization of New-zealand rabbits with aprindine coupled to human serum albumin. Their biochemical characteristics have been determined. Tritiated aprindine was used as radioactive competitor. The cross-reactivity with several metabolites of aprindine was studied too. Finally, the results obtained by RIA in plasma and tissues of dogs were compared to those obtained by gas-chromatography.

The experimental data proposed deals with the adsorption properties of the construction materials used in the dicyclopentadiene (DCPD) production sites. Evaluation of secondary sources of DCPD air contamination is made. Construction materials with the lowest DCPD adsorption are proposed which seem to be of specific practical value in DCPD production sites planning.

The effect of salts, acids, alkali, and buffer solutions on the color development of the Cd-ninhydrin-amino acid reaction has been investigated. Of the salt solutions examined only Cu2+ and Fe3+ interfered with the color yield. Very low concentrations of these ions were sufficient to drastically inhibit color development.

Sulindac, a new anti-inflammatory agent, and its sulfone and sulfide metabolites were conjugated to bovine serum albumin by the N-hydroxysuccinimide active ester procedure. Antiserum from rabbits immunized with each of these haptens exhibited extensive cross-reactivity, precluding differential analyses of the three species by displacement assay without prior separation. Therefore, an analytical method based on a combination of isotope dilution and radioimmunoassay was devised. A known mixture of the three chemical species, each labeled with tritium, was equilibrated with plasma or urine samples, reisolated chromatographically, and quantitated by binding to an appropriate immunoglobulin. The radiolabeled materials thus served as recovery standards as well as labeled antigens for each displacement assay. Sulindac and each of its metabolites in plasma or urine at concentrations as low as 500 ng/sample were differentially determined by this procedure. However, since an extraction is required, several milliliters of plasma can be used for each sample, thus increasing the actual sensitivity of the assay.

Dicyclopentadiene, a waste product of manufacturing at the Rocky Mountain Arsenal near Denver Colorado, has been detected in ground water at this facility. Ground water extracts were analysed by gas chromatography-mass spectrometry (GC/MS) to determine if derivatives of dicyclopentadiene were present in addition to dicyclopentadiene and other chemical wastes. The derivatives thus identified were characterized by GC high resolution MS, deuterium exchange for active hydrogen in the chemical ionization source of the mass spectrometer, and GC/MS following on-column base catalyzed deuteration of enolizable hydrogen. Two ketone derivatives of dicyclopentadiene were identified by comparison with synthetic standards. Ground water derivatives of dicyclopentadiene were compared with mammalian enzymatic metabolites produced in vitro by incubation with immobilized rabbit liver cytochromes P-450. The metabolites were analysed by GC/MS and by GC/MS following derivatization and deuterium labelling. Although not found in ground water samples, the two metabolites were identified as monoepoxides of dicyclopentadiene by comparison with compounds synthesized in the laboratory.

Methods employing solvent extraction, thin-layer chromatography, gas-liquid chromatography, and UV spectrophotometry are described for the quantitative determination of halofenate, cyclobenzaprine and sulindac in rodent diet mixtures. Halofenate was hydrolyzed to its free acid derivative and converted to a methyl ester prior to assay. The drugs were shown to be stable when stored in food mixtures at room temperature for seven days. Diet mixtures containing the three drugs were demonstrated to be uniformly mixed by the procedure employed.

A high-performance liquid chromatographic method using a linear elution gradient has been developed for the analysis of sulindac, sulindac sulfone, and sulindac sulfide in plasma, urine, bile, and gastric fluid. The methodology uses reverse-phase, radial compression chromatography with gradient elution, and UV detection. Sulindac and its metabolites in plasma can be quantitated at 0.25 microgram/mL with a mean CV of 6.0 +/- 2.9%; urine, bile, and gastric fluid (0.5 microgram/mL) yield a mean CV of 5.5 +/- 1.9%.

A GLC method of analysis of a new antiarrhythmic agent, aprindine, is described. The raw material of the new drug substance, supplied as the hydrochloride salt, is dissolved in deionized water, and the base is liberated by a 10% aqueous solution of sodium carbonate. aprindine is extracted with chloroform and mixed with the internal standard, 5alpha-cholestane. GLC is perfomed on a glass column packed with 3.8% W-98 on Chromosorb W-HP. Quantitation is achieved by computer calculation of the peak area ratios. GLC-mass spectral analysis indicates that the observed peak is that of aprindine, with a molecular ion at m/e 322. The retention times of aprindine and the internal standard are 2.0 and 5.8 min, respectively. All synthetic precursors show a shorter retention time than aprindine. This GLC method is applied to the quantitative determination of aprindine as raw material and in capsule and ampul formulations. The method is also used to measure the stability of aprindine to acid, base, dry, heat, refluxing, and UV light and to pH variations.

A simplified method is described for the determination of chlorophacinone, 2-[(p-chlorophenyl)-phenylacetyl]-1,3-indandione, in homogenized mice. Chlorophacinone is extracted with acetonitrile. After Florisil cleanup, the extract is injected into a high pressure liquid chromatograph for reverse phase chromatography on a polar Lichrosorb NH2 (10 micron) column, with a mobile phase of acetonitrile-water (80 + 20). An injection containing 70 ng chlorophacinone produces 1/2 scale peaks at 254 nm with a full scale absorbance of 0.1 unit, an order of magnitude improvement over the sensitivity reported earlier with a 280 nm detector. Six homogenized mice samples and six spiked homogenized mice samples were quantitatively analyzed for trace levels of chlorophacinone by this method. Recoveries from spiked samples, as determined by peak height measurement, were greater than 95%. Mean retention time for the chlorophacinone peaks in all samples was 6.05 +/- 0.05 min. Chlorophacinone levels determined in homogenized whole mouse samples ranged from 0 to 63 ppm.