Characterization of cyclophosphamide (NSC-26271) metabolites and related derivatives by field-desorption and electron-impact mass spectrometry.

Several important metabolites of cyclophosphamide (CP), such as 4-hydroxycyclophosphamide and phosphoramide mustard, some 4-alkyl(aryl)thio derivatives have been investigated by field-desorption and electron-impact mass spectrometry. The structural identification of synthetic compounds and of derivatives, isolated by thin-layer chromatography in vitro, was possible since complementary information can be obtained using the two ionization techniques. Whereas only the field-desorption mass spectra showed more abundant molecular ions, the electron-impact technique revealed a characteristic fragmentation pattern for most of the compounds studied. Examples are given which demonstrate the existence of stereoisomers of CP derivatives using thin-layer chromatography and field-desorption mass spectrometry. The results indicate that field-desorption mass spectrometry is also a particularly appropriate method for the characterization of unstable CP metabolites in vivo.     

Clinical glycopeptide-resistant enterococci isolated from patients after solid organ transplantation

The aim of this study was to confirm the identification and resistance to vancomycin and teicoplanin of nosocomial enterococcal strains using molecular biology methods. Glycopeptide-resistant enterococci (GRE) strains were isolated from clinical specimens of hospitalized patients. Bacterial identification was performed in an automatic ATB Expression system (bioMérieux SA). Susceptibility to glycopeptides was determined by the disc diffusion method and Etest (AB BIODISK, Sweden). We performed polymerase chain reactions (PCR) for Enterococcus faecium and E. faecalis identification and van genes detection. Fifteen GRE strains were cultured over 2 years (2003-2004). Fourteen isolates were highly resistant to vancomycin (MIC range, 128->256 mg/L) and teicoplanin (MIC range, 32->256 mg/L). Twelve strains harbored van A gene (Van A phenotype). Seven isolates were identified as E. faecium and seven as E. faecalis by the multiplex-PCR method. One strain-E. casseliflavus-showed low resistance to vancomycin (MIC 8 mg/L) with retained susceptibility to teicoplanin (MIC 4 mg/L). It harbored the van C2/C3 gene and was identified as the Van C2/C3 phenotype. GRE strains were more often isolated from hospitalized patients in Poland. Constant monitoring by reliable microbiological methods has become necessary to prevent the spread of these strains in the hospital environment.     

Untersuchungen von polymeren im massenspektrometer, 3. Fragmentierungsreaktionen oligomerer benzyle

The thermal degradation of polybenzyls in the mass spectrometer yields oligomeric benzyls with saturated (phenyl-, alkyl-) and unsaturated (quinonemethide) endgroups. To differentiate the thermal and the electron impact induced degradation reactions the fragmentation reactions of oligomeric benzyls of type 1a, b were investigated as models by electron impact. Using low electron energies, alkyl-, α-benzyl-, β-benzyl-cleavage and ortho-rearrangement – specific of 1,2-disubstituted benzyls – were found as the main fragmentations. Isomeric oligobenzyls could be differentiated by the ortho-rearrangement. The fragmentation pathways were confirmed by exact mass measurements and by detection of many metastable transitions using the “defocusing-method”. The influence of different substitution at the aromatic rings and the CH₂-groups on the fragmentation behaviour of the oligomeric benzyls is dicussed.     

Pharmacologically active polymers, 11. Polymeric sulfonamides as potential antibacterials and carriers for antitumor agents

A number of acryl and methacryl derivatives of different sulfanilamides ( 1a—I ) were prepared and polymerized. The fixation of the sulfonamide to the polymerizable group was carried out directly, using the acryl- and methacrylamides, and by means of spacer groups, to favour the enzymatic or hydrolytic release of the drug moiety. Selected sulfonamide types of different pK_A values were used, and the pH-dependant solubility of the corresponding polymers was studied. The monomeric acryloyl and methacryloyl sulfonamides were homopolymerized radically by AIBN. For distribution studies polysulfadiazineacrylamide, ¹⁴C-labelled in the main chain ( 2e' ), was synthesized. Copolymerization with 2-methylsulfinylethyl methacrylate ( 5a ) yielded water soluble polymers of lower toxicity. Eventually biodegradable polymers containing sulfonamide units in the backbone were obtained by anionic polymerization of acryloyl and methacryloyl sulfanilamide. The new monomers and polymers were characterized by elemental analysis, IR- and NMR-spectroscopy, pyrolysis mass spectrometry, and hydrolytic degradation.