Phase I evaluation of zalcitabine administered to human immunodeficiency virus-infected children.

The safety, tolerability, and pharmacokinetics of zalcitabine (ddC) in a single oral dose (0.02 mg/kg) was evaluated in 23 mildly symptomatic human immunodeficiency virus-infected children (mean age, 4.2 years). After administration of ddC, blood samples were obtained at 0.5, 1, 1.5, 2, 4, 6, and 8 h for analysis. The drug was well tolerated and no side effects were noted. Plasma ddC levels were determined by ion spray liquid chromatography/tandem mass spectrometry. ddC was rapidly absorbed, with a mean maximum plasma concentration of 9.3 ng/mL (range, 3.2-14.1) attained within a mean of 1 h (range, 0.5-2.0). Mean elimination half-life was 1.4 h (range, 1.0-3.5), mean area under the plasma concentration-time curve was 25 ng.h/mL (range, 11-37), and mean total body clearance was 14.6 mL/min/kg (range, 8.9-30.6). Plasma concentrations were lower and the half-life shorter in these children than in adults given comparable doses, suggesting that ddC may be cleared more rapidly in children than adults.

N,N-(2,4-dinitrophenyl)octylamine derivatives for the isolation, purification, and mass spectrometric characterization of oligosaccharides.

A simple, sensitive method for the structural characterization of oligosaccharides by fast atom bombardment-mass spectrometry (FAB-MS) has been designed. Oligosaccharides are labeled with a uv chromophore (which also serves as a charge stabilizing group) and with a hydrophobic alkyl tail. The chromophore, a 2,4-dinitrophenyl group, aids uv detection during HPLC and stabilizes negative ion species formed during analysis by FAB-MS. The hydrophobic tail, provided by an octyl group, enhances the surface activity of the analytes and makes them amenable to separation by reverse-phase chromatography using a C18 bonded phase. This method was applied to the structural analysis of the components of a mixture of starch maltodextrins with a degree of polymerization 1-16, to the analysis of the structure of pure maltohexaose, and to a previously characterized oligosaccharide from a Rhizobium capsular polysaccharide. The method gave a good yield of [M-H]- anions for the derivatized compounds, which in most cases were detectable at a level of about 1 pmol. In the case of maltohexaose, four series of sequence anions corresponding to sequential loss of glycosyl residues from the reducing and nonreducing end by different mechanisms were observed. The mixture of derivatized malto-oligosaccharides could easily be separated by HPLC. Based on the relative proportions of the individual oligomers in the mixture calculated from HPLC analysis, even though the higher oligomers were present in amounts of about 0.1%, they could still be easily detected in mass spectra of the entire mixture.(ABSTRACT TRUNCATED AT 250 WORDS)

Selective adsorption of apoferritin on immobilized Fe(III): demonstration of Fe(III) binding sites.

Immobilized metal ion affinity chromatography has been used to demonstrate and partially characterize Fe(III) binding sites on apoferritin. Binding of Fe(III) to these sites is influenced by pH, but not affected by high ionic strength. These results suggest that both ionic and coordinate covalent interactions are important in the formation of the Fe(III): apoferritin complex. This is, to our knowledge, the first demonstration of direct Fe(III) binding to apoferritin. Other immobilized metal ions, including Zn(II), Ni(II), Cu(II), Cr(III), Co(II), and Tb(III), displayed little or no adsorption of apoferritin. The analytical technique of immobilized metal ion affinity chromatography also shows great promise in the purification of apoferritin, ferritin, and other iron-binding proteins.