Improved Quantitative Dynamic Range of Time-of-Flight Mass Spectrometry by Simultaneously Waveform-Averaging and Ion-Counting Data Acquisition

Two different types of data acquisition methods, “averaging mode” and “ion-counting mode”, have been used in a time-of-flight (TOF) mass spectrometry. The most common method is an averaging mode that sums waveform signals obtained from each flight cycle. While it is possible to process many ions arriving at the same TOF in one flight cycle, low-abundance ions are difficult to measure because ion signals are overwhelmed by noises from the detection system. An ion-counting mode is suitable for the detection of such low-concentration ions, but counting loss occurs when two or more ions arrive at the detector within the dead time of the acquisition system. In this study, we introduce a technique that combines two methods to measure target ions with a high concentration difference, i.e., averaging mode and ion-counting mode are used simultaneously for high abundant and trace ions, respectively. By processing waveforms concurrently during data acquisition, one can choose to analyze either or both types of data to achieve a highly quantitative mass spectrum over a wide range of sample concentrations. The result of the argon isotope analysis shows that this method provides a more accurate determination of the isotope ratio compared to averaging mode alone at one-twentieth of the analysis time required by ion-counting alone.

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Mechanism of glass ampoule breakage prevention during the freeze-drying process of sodium thiopental lyophilization products on addition of sodium chloride

Glass ampoule breakage during the freeze-drying process was prevented by the addition of sodium chloride to the formulation of lyophilization products of sodium thiopental. In order to clarify the ampoule breakage prevention mechanism, the physicochemical behavior of the freeze-drying process was monitored by simultaneous XRD-DSC measurements and thermal mechanical analysis (TMA). During the freezing process of formulated solution, the smaller heat of fusion of crystallized ice with the addition of sodium chloride was observed in comparison to that without sodium chloride. Although a greater amorphous portion remained, a higher crystal habit of hexagonal ice was reproducibly observed in the XRD patterns with the addition of sodium chloride during the freezing process. In the measurement of TMA, the scattering of the thermal expansion rate of formulated solution was significantly reduced by the addition of sodium chloride. These observations indicated that the addition of sodium chloride minimized the scattering of the thermal expansion rate and might be a cause for the inhibition of glass ampoule breakage during the freeze-drying process.     

Elucidation of dominant effect on initial bacterial adhesion onto polymer surfaces prepared by radiation-induced graft polymerization

Surface-modified polyethylene (PE) membrane sheets were prepared by the radiation-induced graft polymerization (RIGP) of an epoxy-group-containing monomer, glycidyl methacrylate (GMA). The epoxy ring of GMA was opened by introducing diethylamine (DEA) or sodium sulfite (SS). We examined the properties of these sheets by measuring the amount of grafting polymer, surface roughness and membrane potential, and also investigated the adhesion of five Gram-negative bacteria, Escherichia coli, Pseudomonas aeruginosa, Pseudomonas putida, Pseudomonas fluorescens and Paracoccus denitrificans, onto the prepared sheet surfaces. A linear relationship between the degree of grafting (dg) and surface roughness was observed. Moreover, membrane potential was dependent on the amount of DEA or SS as the ionizable group. These results indicate that RIGP enables the control of the physicochemical properties of such a sheet surface by adjusting dg and the subsequent conversion of functional groups. A batch test on bacterial adhesion onto the sheets clarified that the DEA-containing sheet (DEA sheet) exhibited an adhesion rate constant, k, significantly greater than those of other types of sheet. Clearly, the adhesion rate constant of the DEA sheet increased with dg, indicating that electrostatic interaction is the most decisive factor for bacterial adhesion when it works as an attractive force. Furthermore, the densities of bacteria adhering onto the GMA-containing sheet (GMA sheet) and the SS-containing sheet (SS sheet) were almost the same as that onto a PE sheet, whereas that onto a DEA sheet significantly increased. Thus, the introduction of the GMA- and SS-containing graft chain did not have much influence on bacterial adhesion onto the surfaces, supporting the conclusion that the promotion of bacterial adhesion onto the GMA and SS sheets was due to an increase in surface area resulting from RIGP. Moreover, the scanning electron microscopy images of the sheet surfaces indicate that the conditions and morphologies of initial bacterial adhesion are dependent on surface properties, particularly membrane potential.     

Neutron activation analysis of arsenic in rocks and sediments by direct evolution with chloride- and bromide-condensed phosphoric acid reagents

A simple method is presented for the determination of arsenic in rocks and in sediments by neutron activation. After irradiating a sample it is, without any other treatment, directly heated in condensed phosphoric acid containing sodium chloride or sodium bromide to evolve arsenic as arsenic(III) chloride or bromide. The distillate is absorbed in distilled water, in which arsenic is later precipitated in elementary form by adding hypophosphite to the solution. From arsenite, arsenic(III) oxide, arsenate and arsenic(III) sulphide, arsenic chloride can be evolved with NaCl-CPA reagent, but elementary arsenic and arsenic(V) oxide do not react with it. However, metallic arsenic is found to react with KIO₃-NaCl-CPA and arsenic(V) oxide with the NaBr-CPA, both both evolving arsenic(III) chloride or bromide. Therefore, successive distillations, the first with NaCl-CPA and the second with NaBr-CPA, give a satisfactory means of differential determination of arsenic(III) and arsenate as well as arsenic(V) oxide. For the elementary arsenic a problem still now remains. The chemical recovery of carrier goes well beyond 95%. Part of this work was performed at the Research Reactor Institute, Kyoto University.     

Preconcentration of antimony(III) from water with thionalide loaded on glass beads with the aid of collodion

2-Mercapto-N-2-naphthylacetamide (thionalide) loaded on glass beads with the aid of collodion is used for preconcentration of microgram levels of antimony(III) from aqueous solution. Antimony is quantitatively retained on the loaded beads from 0.4–0.8 mol l^?1 hydrochloric acid solutions; equilibration is achieved within 1 min. The retention capacity of the beads is 0.2 μml Sb g^?1 at 0.6 mol l^?1 hydrochloric acid. The maximum flow rate for quantitative retention is 1.27 ml min^?1 cm^?2. Antimony retained on the column is completely eluted with 10 ml of 6.0 mol l^?1 hydrochloric acid at flow rates<1.9 ml min^?1 cm^?2.     

Effects of liposomal phophatidylserine on phagocytic uptake of liposomes by macrophage-like HL-60RG cells

The purpose of this work is to know the effect of surface properties of liposomes on their phagocytic uptake by macrophages. For this, liposomes were prepared by the Bangham technique from the mixture of phosphatidylcholine (PC) and cholesterol (Chol) incorporated either with phosphatidylserine (PS), phosphatidylethanolamine (PE) or phosphatidic acid (PA). The liposomes thus prepared had diameters in the range between 150 and 260 nm. Electric surface properties of the liposomes and the macrophages differentiated from HL-60RG cells were determined by measuring their electrophoretic mobilities. The phagocytic uptake of liposomes with different contents of PS, PE and PA by macrophage-like HL-60RG cells was investigated by measuring oxygen consumption associated with phagocytic uptake. The phagocytic activity was found to be the highest with the PC–Chol liposomes containing 7 mol% PS, but no significant effects were observed with PA- and PE-containing PC–Chol liposomes. As the uptake was independent of the electric surface property of liposomes, PS was concluded to be specifically important for phagocytic activity of macrophages.     

Interaction of tri-O-methyl-β-cyclodextrin with drugs

Summary The effect of tri-O-methyl--cyclodextrin(methyl--CD) on the partition coefficients of drugs, such as p-nitrophenol, salicylic acid, benzoic acid, and aspirin, was studied at 25°C. The partition coefficients of these drugs were increased linearly with methyl--CD concentration. The increase of partition coefficients was interpreted by the 11 complex formation between methyl--CD and the drug in CHCl₃ phase.The interaction between p-nitrophenol and methyl--CD in solution was studied by UV and PMR spectroscopies. It was concluded that p-nitrophenol is included in the cavity of methyl--CD in both aqueous solution and CHCl₃ solution.Inclusion compounds of these drugs with methyl--CD in the solid state were studied by X-ray diffractometry, IR spectroscopy, and DSC measurements. 11 crystalline inclusion compounds were obtained from hot water. It is also suggested that amorphous inclusion compound was obtained by the grinding of drug with methyl--CD.The dissolution rate and the bioavailability of ketoprofen were significantly increased in the presence of methyl--CD. The bioavailability of ketoprofen after oral administration with methyl--CD to rats was 3.7 times that of ketoprofen alone.     

Separation of technetium from rhenium by liquid-liquid extraction with potassium xanthate

A method is described for separating technetium from rhenium in hydrochloric acid medium by liquid-liquid extraction with potassium xanthate and carbon tetrachloride. The effects of the concentration of various acids, concentration of xanthate, different solvents and diverse ions have been investigated.     

Behavior of fatty acid during the incubation of bovine serum albumin. Entity of the serum albumin resistant to heat

The solution of bovine serum albumin, incubated at pH 9 (0.1 M Tris-EDTA-boric acid buffer in which 0.15 M KCl was contained) and 65 °C for 60 min, gave zones of undenatured monomer (component 1) and aggregates in the pattern of gel electrophoresis. The component 1, isolated from this solution, contained more fatty acids than the original albumin and than the mixture of aggregates. The aggregates contained substantially no fatty acids. This means that fatty acids are released, when the bovine albumin is denatured accompanying with intra- and intermolecular SH/S-S exchange reactions. Taking palmitic acid as a representative of the long chain fatty acid, a model experiment was performed. The bovine albumin, to which 6 palmitic acids were bound, did not cause the SH/S-S exchange reaction and was not denatured on incubation at pH 9 (0.1 M Tris-EDTA-boric acid buffer) and 65 °C. When the solution of “crystalline bovine albumin” (AF_0.9, A: albumin, F: long chain fatty acid) was incubated at pH 9 (0.1 M Tris-EDTA-boric acid buffer) and 65 °C, 20% of the albumin was not denatured even after prolonged incubation. Further, when the component 1 (AF_3.8), isolated from pre-incubated albumin solution, was incubated again at pH 9 and 65 °C, 58% of the albumin was not denatured even after sufficient time of incubation. Quantitative analysis reveals that the bovine albumin containing 6 fatty acids (AF₆) is not denatured at all, and is the entity of the albumin resistant to heat.     

Structure-activity relationships of dopamine- and norepinephrine-uptake inhibitors

Quantitative structure-activity relationship (QSAR) analysis of 3-phenyl-1-indanamines, 1-amino-4-aryltetralins, and 6-phenylpyrrolo[2,1-a] isoquinolines has been performed for catecholamine-uptake inhibition activities. Similar equations were obtained for these series of congeners indicating a common tendency that the increase in hydrophobicity of the substituents on the primary phenyl ring (ring C) enhances the activity, and the important aromatic ring which interacts with the receptor is this ring C. It was also indicated that the effect of the introduction of the second N-methyl group differs depending on the series of congeners. These results were used to characterize a binding model for a pharmacophore, which comprised a phenyl ring and a basic nitrogen. This model defined the necessary three-dimensional features leading to the uptake inhibition, and degree of fitness with this model predicted the strength of the activity. Furthermore, it appeared likely that a substituent existing in a specific region of the inhibitor molecule causes a steric hindrance with the receptor site and reduces the activity.