Particle beam-mass spectrometric analysis of difluorophenyl triazole compounds using normal phase-HPLC

Normal phase liquid chromatography combined with particle beam mass spectrometry has been applied to the analysis of fluconazole, an anti-fungal agent, [2-(2,4-difluorophenyl)-1,3-bis(1H-1,2,4-triazol-1-yl)-propan-2-ol] and a related intermediate, UK-51060 [2-(2,4-difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)-ethan-2-one]. Electron ionisation and chemical ionisation have been investigated in combination with quadrupole ion trap and magnetic sector mass spectrometers and the spectra obtained compared with those for direct probe analysis. A novel method for the introduction of the chemical ionisation reagent gas via the interface is described for particle beam-magnetic sector mass spectrometry. Multi-stage scan routines have been implemented on the ion trap for the selective storage of analyte species and removal of solvent ions. Detection limits for both spectrometers have been determined and are discussed in terms of interface geometry and analyte transport characteristics. Normal phase HPLC on silica provided a good separation of the intermediate from the later eluting fluconazole peak.     

Syntheses and structures of methyltris(pyrazolyl)silane complexes of the group 6 metals

The methyltris(3,5-dimethylpyrazolyl)silane ligand, TpsMe2, was readily prepared by the metathesis reaction of methyltrichlorosilane with 3 equiv of lithium 3,5-dimethylpyrazolate. The octahedral tricarbonyl complexes (TpsMe2)M(CO)3 were synthesized either by ligand exchange with the labile nitrile adducts M(CO)3(NCR)3 (M = Cr, Mo, R = Me; M = W, R = Et) or thermally by direct substitution on the hexacarbonyls M(CO)6 (M = Cr, Mo). The three new complexes were characterized by a combination of analytical and spectroscopic techniques, including electrospray ionization mass spectrometry and single-crystal X-ray diffraction. They are all isostructural and display in the solid state the expected distorted octahedral geometries with facially coordinated tris(pyrazolyl)silane ligands. Crystallographic data were used to calculate the ligand cone angles (251-264 degrees) in (TpsMe2)M(CO)3 and also to estimate a value of 1.59 A for the covalent radius of octahedral W(0).     

Fast, generic gradient high performance liquid chromatography coupled to fourier transform ion cyclotron resonance mass spectrometry for the accurate mass analysis of mixtures

Fast gradient high performance liquid chromatography (HPLC) has been combined with a commercially available Fourier transform ion cyclotron resonance (FTICR) mass spectrometer for the routine and high performance analysis of mixtures. With this combination we were able to separate and detect, under high mass accuracy conditions, a six-component drug mixture in less than 5 minutes. The fast gradients described are now possible due to the development of mechanically robust, ultra pure silica packing materials, which allow relatively high flow rates (ca. 1 mL/min for a 2 mm diameter column). For the six compounds present in the model mixture, relative mass errors of less than 1 ppm were obtained (based on an external calibration) providing sufficient mass accuracy to make unequivocal assignments of empirical formulae. Preliminary results of fast gradient HPLC/FTICR-MS/MS are also shown for the same six-component mixture. Copyright 2000 John Wiley & Sons, Ltd.     

Hemostatic efficacy and tissue reaction of oxidized regenerated cellulose hemostats

Oxidized regenerated cellulose (ORC) has been used as an absorbable hemostat since World War II. In the present study, hemostasis time was determined in a spleen incision model in swine. The effect of mass on absorbable hemostat efficacy and hemostasis time was evaluated by standardizing the ORC materials on a mass basis. The median hemostasis time for a single layer of the new nonwoven ORC was as much as 51 % shorter than woven ORC (P < 0.001). The mean hemostasis time for nonwoven ORC was not affected by the mass of hemostat applied to the wound. The hemostatic efficacy of woven ORC increased with the mass (layers) of hemostat applied to the wound. Nonwoven ORC is significantly faster in achieving hemostasis than woven ORC, and its hemostatic efficacy is not influenced by the mass of material applied. Tissue reaction was minimal and the material was fully absorbed by 14 days.     

On the Heterogeneous Nature of Cisplatin-1-Methyluracil Complexes: Coexistence of Different Aggregation Modes and Partial Loss of NH3 Ligands as Likely Explanation

The conversion of the 1 : 1-complex of Cisplatin with 1-methyluracil (1MeUH), cis-[Pt(NH₃)₂(1MeU-N3)Cl] ( 1 a ) to the aqua species cis-[Pt(NH₃)₂(1MeU-N3)(OH₂)]⁺ ( 1 b ), achieved by reaction of 1 a with AgNO₃ in water, affords a mixture of compounds, the composition of which strongly depends on sample history. The complexity stems from variations in condensation patterns and partial loss of NH₃ ligands. In dilute aqueous solution, 1 a , and dinuclear compounds cis-[(NH₃)₂(1MeU-N3)Pt(μ-OH)Pt(1MeU-N3)(NH₃)₂]⁺( 3 ) as well as head-tail cis-[Pt₂(NH₃)₄(μ-1MeU-N3,O4)₂]²⁺ ( 4 ) represent the major components. In addition, there are numerous other species present in minor quantities, which differ in metal nuclearity, stoichiometry, stereoisomerism, and Pt oxidation state, as revealed by a combination of ¹H NMR and ESI-MS spectroscopy. Their composition appears not to be the consequence of a unique and repeating coordination pattern of the 1MeU ligand in oligomers but rather the coexistence of distinctly different condensation patterns, which include μ-OH, μ-1MeU, and μ-NH₂ bridging and combinations thereof. Consequently, the products obtained should, in total, be defined as a heterogeneous mixture rather than a mixture of oligomers of different sizes. In addition, a N₂ complex, [Pt(NH₃)(1MeU)(N₂)]⁺ appears to be formed in gas phase during the ESI-MS experiment. In the presence of Na⁺ ions, multimers n of 1 a with n=2, 3, 4 are formed that represent analogues of non-metalated uracil quartets found in tetrastranded RNA.