Kiichiro Fujii

Determination of caffeine in saliva by high-performance liquid chromatography: new sampling method for saliva using filter paper.

We report an assay method for the determination of salivary caffeine concentrations by high-performance liquid chromatography. A simple, new method for collecting mixed saliva using a piece of filter paper has been developed. An arbitrary amount of saliva is absorbed and a fixed amount of internal standard is added. The mean coefficient of variation of measurements repeated by changing both volumes absorbed and caffeine concentrations of saliva was 5.6% with this method. The detection limit was determined to be 0.5 microgram/ml. Precision of measurements and recoveries did not depend upon the volume of saliva absorbed. Four volunteers were given a capsule of 230 mg caffeine, and saliva was collected by the ordinary method using chemical stimulation with citric acid and by our filter paper absorption methods; the methods were compared. Salivary caffeine concentrations were always lower than plasma concentrations, and there were no big differences between two methods, although salivary concentrations measured by our method was higher, with a significant difference at 1.5 h after dosing. From the practical viewpoint this method would be convenient and sufficiently accurate.

The concentration of benzyl alcohol in the blood after the injection of ethanolamine oleate.

The concentration of benzyl alcohol (BA) in the blood of the patients after the intravariceal injection of ethanolamine oleate (EO) with meglumine amidotrizoate (EO-MA) for endoscopic sclerotherapy of esophageal varices was determined by GLC method. BA appeared in the peripheral blood immediately after the interavariceal injection of EO-MA, therefore it was found that the leak of BA from the varix occurred very early. But BA disappeared rapidly from the blood (t1/2= 10 minutes). The hemolysis after the intravariceal injection had no relation to the concentration of BA in the blood.The actions of BA and EO on erythrocytes were examined in vitro, and the hemolyzing effect of EO was much stronger than that of BA. From these results, it is thought that the effect of BA on the hemolysis after the intravariceal injection of EO-MA is only a little and the hemolysis probably results from EO.

Effects of several disinfectants against activated sludge at Hamamatsu university school of medicine.

Medium inhibition concentrations (IC50) of disinfectants against activated sludge are in the order of cresol< alkyl di (aminoethyl) glycine hydrochloride< povidone iodine< benzethonium chloride<20% chlorhexidine<5% chlorhexidine<4% chlorhexidine< hexachlorophene< trichlosan. These disinfectants except for trichlosan and hexachlorophene are between organic and inorganic nature according to the Fujitas organic conceptional diagram, and are easily decomposed and removed by activated sludge. In spite of many advantages of cresol asa disinfectant, it tends to be disliked because of its stink. Alkyl di (aminoethyl) glycine hydrochloride showed the lowest inhibition against activated sludge except for cresol, and was estimated as an economical disinfectant.

Quality test of ethanolamine oleate injection.

Quality tests were made on two kinds of oleic acids as raw materials (OA), JIS extra pure reagent (OA-JIS) and guaranteed reagent with content of about 99%(OA-GR), which were used for the material of ethanolamine oleate injection (EO-i). Furthermore, the effect of the difference of OA on the quality of EO-i was studied.The content of peroxide in OA-JIS was higher when it was stored at room temperature than in a cold place. Therefore, it is necessary to store OA-JIS in consideration not only of light and air but of temperature.The pH of EO-i with OA-GR was same as that with OA-JIS, while the viscosity of EO-i with OA-GR was higher. EO-i with OA-GR remained colorless before and after sterilization, whereas in the case of OA-JIS, the pale yellow color became more intense by sterilization. Light and temperature had no effect on the stability of EO-i, e. g., production of peroxide, the content of oleic acid and pH.Although the further comparative study on effectiveness and safety of OA-GR and OA-JIS as the sclerosing agent for esophageal varix is necessary, it is thought, from the above results, that the use of OA-GR is desirable in pharmaceutical aspect.

Content Uniformity of Atropine Sulfate Powders Prepared in Hospital Pharmacy

In the preparation of 0.1% atropine sulfate powder, the effect of the method of preparation on mixing degree, distribution of particle size and component in different particle size was studied by three different methods using tartrazin as a model. Solution mixing method (SMM) as compared with powder dilution method (PDM) and combined method of SMM and PDM, though the component in different particle size was different, gave a good mixing degree which showed small variance at various sampling weight. Distribution of the component in SMM was affected by material or volume of bindet. All the particles in granules which passed through 42-mesh sieve and remained on 200-mesh sieve maintained the 90-110% content when 10% water was used as binder in SMM. Furthermore, packaging procedure had little effect on content uniformity of the powder prepared by SMM and PDM. SMM, if the component in the different size fraction was checked, proved to be a very good method in the preparation of the powders with very low content of active ingredient in hospital pharmacy. Thus 0.1% atropine sulfate powder with good content uniformity was obtained by SMM.

Sterilization of Large Volume Solution by Autoclaving

Temperature of large volume liquid in respective containers (1-3l) was continuously measured with thermocouple under autoclaving in order to determine the time for the temperature of the liquid to reach 115°. Sterilization temperature, regardless of a number of containers per load, was uniform even at various locations of the containers in the chamber. In spite of rapid rising and lowering of temperature, exhausting time was so long that the ingredients were decomposed. The size of containers was the most important factor in raising liquid temperature to 115°; 40 min for the 3l container. The degree of sterilization was estimated from Log Inactivating Factor (LIF) based on a first-order reaction and the course of temperature under autoclaving. LIF was very useful for the determination of sterilization time, because it considerably agreed with a number of surviving B. stearothermophilus. The sterilization time of the 3l container was thus determined at 60 min corresponding to LIF 11.

Compatibility of Bricef Dry Syrup with Mixed Solutions

Compatibilty of Bricef Dry Syrup (cefatrizine oral suspension) with mixed solutions which were often pre scribed in our hospital was investigated in terms of changes in external appearance pH and residual potency of cefatrizine (CFT). These changes were checked immediately after and 1, 3, 5, 7 and 14 days after mixing. The results showed lowering, to some extent, of CFT potency in relatively high pH region. Especially, when dry syrup was mxed with an alkaline solution, CFT potency reduced significantly within 24 hours at room temperature. These results suggest that careful attention should be paid to the above combination since a risk of incompatibility may be involved.Color of suspensions of a few preparations changed during the storage. The change in color should be avoided to prevent anxiety in patients, though its correlation with stability of CFT is not clear. In combiantions with other solutions, the change in appearance, pH and potency of CFT was small, suggesting that such combinations be clinically recommendable.