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Biomedical subjects

C M Deber

Publications and source records attributed to C M Deber.

At least 91 records · Page 5Linked to original sources

Gas chromatographic/mass spectrometric analysis of methylphenidate (ritalin) in serum.

A gas chromatographic/mass spectrometric (GG/MS) procedure for the determination of methylphenidate in 1 mL of serum or plasma is reported employing ethylphenidate as internal standard. A 50/50 (V/V) mixture of benzene and hexane is used to extract the methylphenidate and ethylphenidate from plasma. After evaporation of solvent the residue is redissolved in 50 microL hexane. Methyl- and ethylphenidate are then derivatized by the addition of 50 ML of trifluoroacetic anhydride and the TFA derivatives are injected into a quadrupole GC/MS for analysis. This method has a lower limit of sensitivity for methylphenidate of 2.0 micrograms/L. The between-day precision study yielded coefficients of variation of 10.4% and 14.8% at methylphenidate concentrations of 25.6 and 5.2 micrograms/L respectively. The assay has been used to investigate the pharmacokinetics of methylphenidate administered to 6 children for treatment of hyperkinesis. The study yielded ranges for volume of distribution, elimination half-life, and total body clearance of 5.0-6.8 L/kg, 1.6-2.7 hours, and 1.4-2.9 L/kg-hr respectively.

Adolescent↗

Peptide models for protein-mediated cation transport.

Substances which can perturb the transmembrane cation balance in a predictable manner have wide-ranging uses in the study of cellular processes. We have undertaken to examine transmembrane calcium transport on the molecular level through the design and synthesis of a series of ionophoric peptides as models for protein-mediated calcium transport. General mechanisms for carrier-mediated membrane transport are discussed. Cation transport profiles are presented for transport by synthetic peptides of structure cyclo(Glu(OR)-Sar-Gly-(N-R1)-Gly)2, where R = benzyl ester or H; R1 = n-decyl or cyclohexyl. Transport of physiologically abundant cations across "liquid membranes" in Pressman cells mediated by cyclo(Glu-Sar-Gly-(N-decyl)Gly)2 was observed to be essentially calcium specific, as long as calcium ions were present in the system. Multilamellar and unilamellar phosphatidylcholine vesicles were each found to be emptied of internal 45Ca2+ ions upon addition of cyclo(Glu(OBz)-Sar-Gly-(N-cyclohexyl)Gly)2 to the vesicle suspension. The results are compared with the naturally occurring calcium ionophore A23187.

Biological Transport, Active↗

Ionophore A23187. Solution conformations of the calcium complex and free acid deduced from proton and carbon-13 nuclear magnetic resonance studies.

Proton and carbon-13 nuclear magnetic resonance (NMR) spectra have been used to deduce possible biologically relevant conformations of ionophore A23187 as the free acid, and as the calcium complex, in solution. By analysis of coupling constants and dihedral angles obtained from 270-MHz proton NMR, A23187 free acid molecules and individual A23187 anions which comprise the calcium complex are found to differ principally by the rotational state of a carbon-carbon single bond near the benzoxazole ring. Proton Tl relaxation data and measurements of rotational correlation times confirm the dimeric nature of the calcium complex vs. the free acid monomer. Using the deduced pseudocyclic conformation for the A23187 anion, in conjunction with model-building studies, a conformation for the calcium complex is proposed, in which the benzoxazole carboxylate oxygen, the ketopyrrole oxygen, and the benzoxazole (ring) nitrogen atom of each molecule are the major participants in calcium binding. Additional stabilization of the structure is possible through the formation of a postulated hydrogen bond bridge between the pyrrole NH proton and benzoxazole carboxylate oxygen.

Anti-Bacterial Agents↗