M. Anbar

Bioavailability of imipramine tablets relative to a stable isotope-labeled internal standard: Increasing the power of bioavailability tests

A new methodology for comparative bioavailability testing is described in which each drug formulation is compared with a stable isotope-labeled variant of the drug that is consumed orally in solution at the same time the tested formulation is ingested. The methodology is used to determine the comparative bioavailabilities of two commercially available brands of imipramine hydrochloride. The power of the new methodology to detect differences between drug formulations, when, in fact, such differences exist, is shown to be superior to that of conventional bioavailability tests.

Potential Use of Organic Polyphosphonates as Adhesives in the Restoration of Teeth

Currently used dental restorative materials generally do not adhere to dentin or enamel. This lack of adhesion necessitates undesirable undercutting of cavities to permit mechanical retention of fillings. Since enamel and dentin consist principally of hydroxyapatite, which is a calcium phosphate mineral, phosphonate-containing polymers could adhere to teeth by forming chemical (ionic) bonds between the calcium of hydroxyapatite and the phosphonate groups of the polymer, which would increase the adhesion of the restorative material to the tooth and prevent seepage of fluids into the restorativetissue interface. Such a polymeric system could be used in bulk as a restorative material, or as an adhesive between the tooth surface and a conventional polymeric restorative. Hydroxyapatite crystals carry three P043ions per unit cell that are readily exchangeable by other phosphate ions. This is easily shown by isotopic exchange Phosphonate ions, RP032-, can exchange the phosphate ions on hydroxyapatite crystals. The equilibrium for the latter exchange reaction, however, strongly favors the P043ion at the surface. This lower affinity of phospho-

Organic Polymeric Polyphosphonates as Potential Preventive Agents of Dental Caries : In Vitro Experiments

Organic polymeric polyphosphonates adsorb on enamel surfaces in the form of a monolayer and inhibit calcium and fluoride ion transport but not that of phosphate ions. The polymers investigated include phosphonated polyethylene, polyvinylphosphonate, and polyvinylbenzylphosphonate. The adsorption of proteins on enamel, as exemplified by human serum albumin, is diminished and the adsorbed protein is more readily desorbed from surfaces with polymeric polyphosphonates. These jendings may offer an explanation for the anticariogenic effect of polymeric polyphosphonates.

Characterization of coal-liquefaction products by molecular-weight profiles produced by field-ionization mass spectrometry

Abstract Field-ionization mass spectrometry, which produces fragmentation-free mass spectra, is being applied to the analysis of coal-liquefaction products. Using a new highly efficient and sturdy field-ionization source, samples of various coal-liquefaction products have been successfully analysed and their molecular-weight profiles determined by the integrating multiscan technique. The range of applications of this novel analytical technique to research and development of coal-liquefaction processes is discussed.

A combined field ionization-ion kinetic energy spectrometer for multicomponent mixture analysis

Abstract A combined field ionization-collision-induced dissociation instrument has been constructed that will allow the determination of structure of individual components in a complex mixture. A high transmission mass analyzer, differentially pumped collision cell and a spherical electrostatic analyzer are employed to allow collisional spectra to be recorded using samples containing approximately 1 μg per component.

Existence of H2−, a relatively long‐lived doubly charged negative atomic hydrogen ion

Doubly charged negative hydrogen ions H2− and D2− have been indirectly observed in a tandem mass spectrometer using a hollow cathode duoplasmatron ion source. The half‐life of these doubly charged ions, determined in a number of drift time experiments, is 23±4 nsec. The existence of these ions is concluded from a velocity, momentum, and energy analysis of hydride ions produced in the autodetachment process: X2−→X−+e (X=H,D).

An integrating multiscanning field ionization mass spectrometer

Abstract A mass spectrometer comprising a field ionization source and a modified Wien filter is described. This instrument has been developed for analytical applications in the mass range 100 ≦ M ≦ 400 a.m.u., which is scanned repeatedly by varying the E field of the velocity filter synchronously with an integrating multichannel analyzer. The magnetic field is held constant. A linear relationship between mass number and channel number is achieved electronically. Ion optics and electronic circuitry are described. Performance is exemplified by unfragmented molecular ion spectra of mineral oils.

Localized Fluoride Release from Fluorine-carrying Polyphosphonates

Fluoride release from fluorine-carrying copolymers of vinylphosphonate induced by calcium apatite and tooth enamel has been investigated. Fluoride ions were determined potentiometrically in the study of calcium hydroxyapatite, and Auger spectroscopy was used to study the fluoride release to enamel. The adsorbed copolymer of vinylphosphonic acid and vinylphosphonyl thiofluoride was shown to release fluoride to calcium hydroxyapatite and to enamel. The oxygen analog has shown a similar behavior with calcium hydroxyapatite, but not with tooth enamel. The results suggest a potential application of such copolymers as caries preventive agents which combine the effects of polyphosphonates and of fluoride ions.

Improved Adhesion of Acrylic Restorative Materials to Dental Enamel by Precoating with Monomers Containing Phosphonate Groups

The adhesion of acrylic composite restorative materials to etched dental enamel is increased by a factor of two or more when the enamel is coated with a thin layer of vinylbenzyl phosponic acid (VBPA) prior to forming the enamel-restorative bond. The present results support the suggestion that the enhanced adhesion is attributable to bonding between calcium ions in the enamel surface and phosphonate groups in the VBPA.

Adsorption of Polyphosphonated Polyethylene on Enamel of Teeth

Phosphate ions, which are one of the main constituents of the mineral phase of bone and teeth, are incorporated into the bone mineral and are chemisorbed by it, as demonstrated by 32P-labeled phosphate. A molecule that carries a large number of -POgroups (eg, a polyphosphate ion) and thus is a polyfunctional complexing agent, will show an even higher tendency for chemisorption. Consequently, if organic polyphosphate or polyphosphonate ions carry a large number of -POgroups, they will adhere to hydroxyapatite crystals almost irreversibly. Organic polyphosphates, (ROPO3H)n, are much more stable under physiologic conditions and thus more suitable for practical applications. Polyalkyl polyphosphonates, [(CH2)mCHPOa3 H-]n, (PP) accumulate in bone and thereby inhibit the accretion and resorption of calcium and phosphate ions (M. ANBAR, C. FELDMAN, S. LINDLEY, and P. WOLF, Experientia, in press). Acrylic copolymers of vinyl phosphonic acid, to be used as dental restorative materials, have been shown to have high mechanical adhesion to enamel. It also has been shown that the adsorption of alizarin in vitro onto human teeth treated with PP is diminished significantly (M. ANBAR, unpublished results). The latter two findings indicate that polyalkyl polyphosphonates adsorb onto enamel. In this study direct evidence is presented, by use of a 32p_ labeled PP, that these polyelectrolytes adsorb strongly onto enamel. 32P-labeled PP (32PP) was synthesized by oxidative phosphorylation of polyethylene by PCI3, according to a procedure of Leaffer and Anbar (J Labelled Compounds, Experientia, in press). The PP had a molecular weight of 7,500 and contained 12% P at a specific activity of 25 tic/mg P. Crowns of bovine (1 year) canines (Epoxilite Corp, Los Angeles) were stored at 10 C under water. Before experiments, all cut, pulp, and dentin surfaces of the teeth were wiped dry, filled, and coated with clear epoxy resin (Bordens) and after curing for 2 hours at room temperature were reimmersed in water for 48 hours before the experiment. Teeth were immersed in aqueous solutions (pH, 7.3 to 7.5) containing different concentrations of 32pp for predetermined periods; radioactivity was measured, after washing with distilled water and wiping, in a NaI(Tl) welltype scintillation counter. Parallel experiments with 32P-labeled phosphate ions and 36C1labeled chloride ions were done as controls. In a different series of experiments, the kinetics of resorption was measured by immersion of teeth with absorbed labeled polyphosphonate, phos-