Hiroe Kishi

High-performance liquid chromatography of coenzyme Q-related compounds and its application to biological materials

A convenient and precise method for the separation and determination of coenzyme Q (CoQ)-related compounds (CoQ homologues, plastoquinone-9, ubichromenol-9, etc.) was developed using high-performance liquid chromatography (HPLC). All compounds tested were separated using a reverse-phase column with a suitable mobile phase and detected at a wavelength of 275 nm. CoQ extracts in plasma and erythrocytes were purified by thin-layer chromatography prior to HPLC analysis, but such purification was not necessary when determining CoQ in urine and tissues. Hydroquinone forms of CoQ existing in animal tissues were oxidized to the corresponding quinone forms with potassium hexacyanoferrate(III). This HPLC method was applied satisfactorily to the determination of the contents of CoQ homologues in human and animal samples. CoQ10 was the only homologue detected in human samples, and CoQ8, CoQ9 and CoQ10 were native homologues of CoQ in rat tissues. Ubichromenol-9 and plastoquinone-9 were not detected in these samples.

Delayed neurotoxicity produced by an organophosphorous compound (Sumithion)

A case of late-onset manifestation of organophosphorous insecticide poisoning is described. The patient was a 70-year-old female who ingested 40ml Sumithion emulsion (50% fenitrothion). At first, no toxic symptoms were apparent. However, 48 h after ingestion certain signs became apparent. An impediment in consciousness was observed. Fasciculation and muscular weakness were noted, while plasma and urinary 4-nitro-3-methylphenol (NMC), the degradation product of Sumithion, reached a maximum. Neither atropine sulfate nor PAM (pyridine 2-aldoxime methiodine) were effective. For 3 weeks the patient required ventilatory support, and consequently her muscle strength and neurological status gradually recovered with falling NMC levels.

Vitamin A and E Requirements During Total Parenteral Nutrition

Studies were undertaken to determine rational dosages of vitamin A and E during long-term total parenteral nutrition (TPN). Four kinds of vitamin prescriptions containing different amounts of vitamin A and E were prepared from commercially available products and/or hospital pharmacy products. Patients were divided into four groups according to the vitamin prescription used. Plasma vitamin levels of different patient groups were determined by a modified fluorimetric method and were compared with those of a normal subject group. The stability of vitamin A and E in TPN solution after admixing was determining by measuring the remaining vitamin contents by high pressure liquid chromatography. From the results, it was concluded that 1) about 50% of vitamin A was decomposed by sunlight (about 2000 lux) 3 hr after admixing and an orange-colored vinyl cover could protect its photodecomposition; 2) vitamin E was stable at any condition tested; 3) 2500 IU of vitamin A and 15 IU of vitamin E could meet the daily requirements; 4) the plasma levels of vitamin A and E were correlative (p less than 0.01); and 5) concomitant administration of vitamin E was essential to keep the poorer level of vitamin A in plasma.

Pharmaceutical evaluation of change of phenytoin dosage form from powder to fine granule.

Phenytoin (PHT) fine granule, which has the same bioavailability as the tablet, has recently been marketed. We projected a change of PHT dosage form from usual powder to fine granule. In view of the fact that 97% of PHT products prescribed and marketed are available in fine granules, 50% PHT preparations were produced in hospital pharmacy. 5 kinds of preparations using various lactoses as diluents were prepared and tested for their quality. Among them, the preparation from Aleviatin fine granule passing through a 42-mesh sieve and EFC lactose showed the best results in the mixing property and various sense tests. The change to this dosage form and its bioavailability tests were carried out by a cooperation of doctors and pharmacists. Serum PHT levels of all patients, assayed by EMIT method, showed a 20% to 30% increase after the administration of the new preparation (50% PHT fine granule with EFC lactose).

Toxieity of Swallowed Micra-batteries

With recent advances in electric technology, about 300 million micro-batteries are manufactured annually in Japan, being widely used for childrens electric toys as well as for cameras, watches, calculators, and hearing aids. The accidents of ingestion of the batteries by small children have often been reported in the past one year. These batteries consist of an outer nickel-plated container (cathode) and a cap (anode) which are jointed by a plastic seal. They usually contain highly concentrated potassium hydroxide, mercury salts, zinc and some others depending on the type.This paper describes the process of corrosion and leakage of the batteries in several kinds of solutions. It also analyzes the 11 cases of inadvertent ingestion of the batteries which our poison informatiqn services accepted in the last half year.

Stability of Ascorbic Acid in Total Parenteral Nutrition Solutions

The stability of ascorbic acid (AsA) in total parenteral nutrition (TPN) solutions was investigated by using high performance liquid chromatography. In the study, a multiple vitamin injection set (PV-123) was used as a source of AsA. This set contains 13 different kinds of vitamins and the amount of AsA is 100mg/set. Although AsA was oxidized markedly to dehydroascorbic acid in electrolyte infusion solution, it was rather stable in TPN solutions exposed to indoor diffused light (2, 000lux, 6hrs.). Especially, AsA in PV-123 was significantly stable in the certain TPN solutions even after the addition of trace element injection for TPN (IVH-M2). Such an effect suggested that the certain TPN solutions contain the antioxidizing agent and have the low amount of partial oxygen dissolved.AsA in TPN solutions, which were stored in refrigerator for 1 week, was kept almost stable. However, the residual amount of AsA reduced fairly after 7 days on the addition of IVH-M2 to these solutions.Multivitamin injections, which contain B1, B6, B12, are added frequently, with AsA, to electrolyte infusion solutions. AsA was degraded by hydroxocobalamin, but was stable in the presence of cyanocobalamin in infusion solution. Multivitamin injections did not significantly influence on the stability of AsA in TPN solutions when stored in refrigerator.

Preparation of Iron Injection for Intravenous Hyperalimentation at Hospital Pharmacy and Its Stability in Infusion Solution

For the purpose of medical treatment or prevention of anemia, the iron injections for intravenous hyperalimentation (IVH) prepared at hospital pharmacy were investigated in Osaka University Hospital. Various stabilizers of iron colloid were comparatively examined and sodium chondroitin sulfate (CSA-Na) was chosen for its high stability in infusion solution. Soluble iron concentration in injections and infusion solutions was determined by atomic absorption spectrophotometry. The CSA-iron injection for IVH contains in each ampule 2mg of iron and 10mg of CSA-Na. The preparation methods are as follows: i) add reciprocally iron (FeCl3·6H2O) solution and sodium hydroxide solution to CSA-Na solution, ii) adjust pH value to 6.0, iii) filter by 0.45μm membrane filter, iv) sterilize with steam at 121° for 20min. This iron injection was stable for 72 hours in IVH solution.

Screening Test of Microbiological Status of Solutions for Internal Use and of Radiopaque Media by the Method Described in PAB Notification No.297

The microbial quality control of 41 solutions or suspensions for internal use and of 8 radiopaque media was investigated by the test method described in PAB Notification No.297 (valid on April 1, 1976). All of the 49 pharmaceutical products tested met the standard requirements provided in the Notification, so that they are considered to be under good microbial quality control. Most of the sample solutions of radiopaque media were turbid and were difficult to be put to the test for microbial count. In this point, the test method for the microbial count is desired to be improved. A test method of estimating the possible antimicrobial activity of products is also desired to be standardized, because the antimicrobial activity may affect the final results of the tests in the Notification.

Preparation and Quality Tests of Trace Element Injections for Intravenous Hyperalimentation

(IVH) were prepared and quality tests were conducted on their content uniformity and sterility. The composition of the injections was: IVH-Zn: Zn 20ƒÊmal; IVH-M: Zn 20 μmol, Mn 40ƒÊmol, Cu 5ƒÊmol, I 1 ƒÊmol. The ingredients were filtrated through 0.45ƒÊm membrane filter, filled and wet-sterilized at 121•‹ for 20 minutes. The content uniformity was determined by Atomic Absorption Spectrophotometry. The standard contents of the elements in the injections were determined in the range of 90 to 110w/v%. All lots were negative to Sterility Test (J. P. IX).

Evaluation of Microbial Contamination of Pharmaceutical Products

Twenty one pharmaceutical products which had shown a positive reaction of microbial contamination in all of the 5 culture media in the previous sterility test were selected for this test. This paper compares the levels of microbial contamination in the latest test with those in the previous test conducted 3 years before, and also analyzes the tendency of the recent quality control of pharmaceutical products in relation to microbial contamination. In the latest study, total aerobic microbial count of more than 10000/g was observed in 3 of the 21 products, showing the same incidence as in the previous test. Total aerobic microbial count of less than 1, 000/g was observed in 15 products, as compared to 10in the previous test. Coliform organisms were detected in 2 products, compered to 6 in the preceding study.