Synthesis and biological properties of the lipophilic technetium-99m complex 99mTc(acac)3.

In the development of technetium-99m radiopharmaceuticals for the evaluation of regional cerebral perfusion, one series of complexes that has remained unexplored is the neutral lipophilic tris complexes formed with beta-diketonato ligands. The prototype complex of this series, tris(2,4-pentanedionato) technetium(III), has been prepared via a new synthetic route and chemically characterized using 99Tc and the biodistribution of the no-carrier-added 99mTc complex has been determined. The 99mTc complex was found to be distributed throughout the body with persistent high blood levels indicative of a high degree of protein binding. The primary route of excretion was the hepatobiliary system as indicated by the appearance of 99mTc in the gut and feces at longer sample times post-injection. Although this complex was not retained by the brain, it does provide a starting point from which a more effective agent might be developed.

In-beam electron ionization mass spectra of penicillins.

The characteristics of in-beam electron ionization mass spectra of 6-aminopenicillanic acid and several penicillins, which yield no detectable molecular ion peaks using a conventional direct-insertion probe, have been established. The spectra of all compounds studied, with the exception of amoxicillin, exhibited molecular ion or (M+1) peaks with spectral features similar to the reported methyl ester or amide derivatives of the compounds. The fragmentation of penicillin G on electron impact under in-beam conditions can be described on the basis of data from mass analyzed ion kinetic energy spectrometry. A desorption technique utilizing polyethylene glycol 4000 was used as a means of obtaining satisfactory spectra of ampicillin and amoxicillin.

Thermal decomposition of propoxyphene during GLC analysis.

The decomposition products of propoxyphene during GLC were prepared on a larger scale by heating propoxyphene hydrochloride in the presence of glass wook. They were identified by mass spectrometry and NMR spectroscopy as two isomeric diphenylbutenes and two isomeric products formed by loss of propionic acid. On-column decomposition of proxyphene can be prevented by injection of the compound in solution in a silylating agent.

Identification tests for propantheline bromide.

A method is described for the isolation and identification of propantheline bromide from bulk drug substances and dosage forms, both alone and in combination with other drug substances. The method permits the specific identification of the intact drug substance, using both infrared spectroscopy and thin layer chromatography.

Chemical data: an essential tool in the regulation of drugs.

How the Bureau of Drugs laboratories and offices obtain chemical data from the scientific literature, from user complaints and product defect reporting systems, from the drug manufacturers, from analyses of drug samples collected from the market, and from analytical research are described. The chemical data thus educed have been used successfully in developing new analytical methods, in establishing better specifications of drug quality, in removing adulterated drugs from the marketplace, in successfully prosecuting purveyors of substandard drugs, and in general assuring that consumers are provided with safe and effective drugs of high quality.

Crystal and molecular structure of quinidine.

The structure of the free base quinidine was determined by single crystal X-ray diffraction. Quinidine crystallizes from absolute ethanol as the ethanolate, with the molecular formula C20H24N2O2.C2H6O and molar mass 370.491 units. It crystallizes in the orthorhombic space group P212121 with unit cell dimensions a = 1321.1(3), b = 989.3(2), and c = 1651.5(3) pm. The measured density was 1.15 g/cm3; the density calculated for Z = 4 was 1.164 g/cm3. The diffraction data were collected by using MoKalpha radiation. A final R value of 0.055 was obtained. Evidence for intermolecular hydrogen bonding was found. The crystal analysis is in agreement with the structure proposed by other methods. The absolute configuration is based on the published structure of 10-bromo-10,11-dihydroepiquinidine.

Proton magnetic resonance spectroscopic determination of disulfiram: collaborative study.

A proton magnetic resonance spectroscopic method for determining disulfiram in the bulk drug product and in the formulated material was collaboratively studied. The method depends on the use of chloroform-d as a solvent and hexamethylcyclotrisiloxane as the internal standard. No interference from tablet excipients was observed. The method is rapid and specific. Eighteen laboratories analyzed duplicate samples of a bulk drug product, a 250 mg tablet composite, and a 500 mg tablet composite. The average per cent results and standard deviations were 99.7 +/- 1.4, 100.9 +/- 2.0, and 99.9 +/- 2.2, respectively.

Mandelonitrile beta-glucuronide: synthesis and characterization.

Mandelonitrile beta-glucuronide, the compound patented as Laetrile, has been synthesized from rabbit liver uridine diphosphate-glucuronosyl transferase immobilized on beaded sepharose, has been analyzed by thin-layer chromatography, nuclear magnetic resonance, and gas chromatography-mass spectrometry, and has been tested for cytotoxicity and mutagenic activity with Salmonella typhimurium strains TA 98 and TA 100. Several commercial laetrile preparations contained no glucuronide; they contained amygdalin and neoamygdalin instead. Mandelonitrile, mandelonitrile glucuronide, and a mixture of amygdalin and neoamygdalin were each found to be mutagenic.

Synthesis of spin-labeled nitroxyl esters of steroids.

The preparations of spin-labeled nitroxyl esters of prednisone, cortisone, deoxycorticosterone, and cholesterol are described. The ESR spectra indicate that the esters of the three steroids with an oxygen atom at the 11 position have narrower band widths than those with only protons at that position. Mass spectral, chemical, and ESR studies confirmed the structures and purity of the compounds prepared. Reaction of four esters with prednisone antibodies showed reversible binding and large crossover binding.

Mass spectral coding technique for identification of drugs and related compounds in reference compendia.

A modification of the spectral abbreviation technique originally described by Hites and Biemann is proposed for identifying compounds through a coding of mass spectral data. Data from 2 closely related compounds (trimethadione and paramethadione), acquired by using 3 instruments, are presented. The technique appears to overcome observed differences in low resolution spectra when the same compound is analyzed by electron impact on mass spectrometers differing in design, manufacturer, principle of ion separation,, and operator. A list of spectra coded by this technique could constitute a rapid manual system of reproducing mass spectral data, using the significant high mass ions of low abundance as well as the frequently more abundant lower mass ions. This system is compared with existing systems.

Infrared spectrophotometric analysis of medicinal gases for trace impurities.

The feasibility of examining medical gases for trace impurities, using an infrared spectrophotometer in conjunction with a 10 m gas cell, was investigated. Many of the impurities for which the USP includes limits were detected and measured at concentrations at or below those permitted by the USP; these include sulfur dioxide, carbon dioxide, carbon monoxide, and water. However, others (hydrogen sulfide, nitric oxide, and nitrogen dioxide) were not detected at these levels by this technique. Methane was found at low levels in some samples.

Determination of methyl methacrylate in surgical acrylic cement.

A methyl methacrylate cement used in hip surgery as well as in dentistry was identified and quantitatively analyzed for its monomer content in starting materials and in the finished cement by proton magnetic resonance spectroscopy. IR data indicated that the monomer continued to escape from the product after it had hardened. The presence of 21% methyl methacrylate monomer relative to the polymer was demonstrated at the time the cement normally would be inserted into the body.

Configuration of dienestrol.

Uncertainty concerning the configuration of dienestrol was resolved by a detailed spectrochemical investigation, including single-crystal X-ray diffraction, of the active drug and its stereoisomers. A symmetric structure in which the phenyl and methyl groups are cis about each double bond is unambiguously assigned.

The analysis of pharmaceuticals by combined gas chromatography-mass spectrometry. I. The analysis of a medicated aerosol spray.

A medicated aerosol product was qualitatively analyzed by combined gas chromatography-mass spectrometry. The data were processed by a minicomputer. Ten of the 11 peaks in the gas chromatogram were identified with the assistance of the National Institutes of Health/Division of Computer Research and Technology/Chemical Information System mass spectral search system. The unidentified peak is probably a member of the terpene class. The aerosol propellants were also partially analyzed by infrared spectrophotometry.