We evaluated two assay methods to determine serum disopyramide concentrations in application to the practice of medicine. The methods are high-performance liquid chromatography (HPLC) and enzyme immunoassay (EMIT).
In HPLC method disopyramide was separated on a reverse phase. The degrees of precision in HPLC method and EMIT method were less than 5.2% and 5.7% in C. V., respectively. Both methods gave excellent reproducibiliy with C. V.: less than 5.7% in HPLC method and 5.5% in EMIT method. The recovery ratio ranged from 98.0 to 100.7% in HPLC method and from 102.1 to 103.8% in EMIT method. Disopyramide concentrations in sera of healthy subjects and those of patients measured by HPLC method correlated well with those by EMIT method. We conclude both HPLC and EMIT methods are suitable in the routine practice of medicine for measurement of serum disopyramide concentrations.

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Plasma theophylline concentration was determined by immuno-precipitation inhibition technique (i-PiT system). Immuno-reaction is dependent on incubation time and temperature, and therefore it is necessary to optimize the reaction. Within-day and between-day variances (C. V.) of analysis on 3 levels were less than 10%. The results of dilution test and recovery test were good. Forty-two plasma specimens of patients receiving theophylline therapy were studied by i-PiT system and high-pressure liquid chromatography (HPLC). The correlation coefficient was 0.988 and the regression line gave y= 0.978 x+0.918 (y: i-PiT, x: HPLC).

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An investigation was attempted to determine the effects of triethanolamine, monoethanolamine, ammonium sulfate, hydrazine hydrate and hydroxylamine hydrochloride on the enzyme activity of glutamic acid dehydrogenase which is a pyridine enzyme playing an important role in the oxidation and reduction of living bodies. Results obtained were as follows:
1) Sodium glutamate and DPN were dissolved in a potassium phosphate buffer solution. Immediately after addition of the enzyme solution to the buffer, each of the above reagents in different concentrations was added to determine the effects of the mixtures on the enzyme activity for 6 minutes. Triethanolamine, monoethanolamine and hydrazine hydrate enhanced the enzyme activity. The largest increase, about 46%, was observed in the monoethanolamine mixture at the final concentration of 3.3×10 ^-2 M. The second largest increase was found in triethanolamine and the smallest in hydrazine hydrate.2) Hydroxylamine hydrochloride and ammonium sulfate inhibited the activity of glutamic acid dehydrogenase; ammonium sulfate inhibited the enzyme activity by about 50% at the final concentration of 5.0×10 ^-3 M, and the percentage was higher than that caused by hydroxylamine hydrochloride.

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A high performance liquid chromatographic (HPLC) method was developed for the determination of physostigmine (PS) in the presence of degradation products, and the stability of PS in aqueous solution was also examined by this method.
Sufficient separation was effected on an ODS column with an eluent of CH₃CN: 0.5% CH₃ COONH₄ aq.(70: 30). Tolperisone HCl was most suitable of all drugs studied for the internal standard. Coefficient of variation for determination of PS was less than 1%. HPLC method was better, in its simplicity and accuracy, than other methods (U. S. P. methods etc.).
PS in buffered aqueous solution was most stable at about pH 3, when heated in boiling water. Although PS solution in anaerobic condition was almost colorless and produced rubreserine and unknown decomposed substance not recognized in aerobic condition, no difference could be detected for the degradation rate of PS.
It was found that N₂ exchange retards the discoloration, but it has no effect on the stability of PS solution.

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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.

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The stability of trasylol in ointments with various bases has been investigated. Trasylol content in the ointment with purified lanolin as its base was found to decrease markedly during storage at room temperature, while the other ointments with CMC-Na, cholesterol and white petrolatum as their bases gave neither any visible change in appearance nor any decrease in trasylol content after storing at room temperature for 8 weeks.

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Recently, we have found 3 different values, θ, RHs and RHs', to represent hygroscopicity of pharmaceutical preparations in powder or granule, and recommended that those preparations should be stored under relative humidity (RH) lower than RHs to protect them from environmental water.
The effect of storage on degradation of active ingredients in dry syrup (DS) preparations was examined in the present study. The same DS preparations as the previous work, with and without addition of sulpyrine powder, were stored on 7 grades of RH at 30°. Each active ingredient was determined by HPLC after storage for 0, 3, 7 and 14 days.
Sulpyrine stimulated degradation of the active ingredient in DS preparations tested except F, because sulpyrine increased moisture absorption of the DS preparations and caused interaction with the active ingredients. When stored at RH lower than RHs, DS preparations except B and C showed the degradation less than 5% for up to 7 days, and those except B, C and D for up to 14 days. It is concluded that powders and/ or granules should be stored at RH lower than RHs.

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On the matter of division of powder-granule combination preparations into a prescribed dosage unit, the Guideline for Dispensing by the Japan Pharmaceutical Association recommends separate division of powder and granule (two-step dividing method) rather than the division of the 2 components at the same time (one-step dividing method). As discussed in the previous paper, however, the two-step dividing method is not adequate when the combination preparations are divided by machine, not by hands.
In this study, the one-step and two-step dividing methods were compared in terms of the content uniformity of the powder component in the sample after division by machine. The machine used was the modified type (L-2) of Konishi KC-787-K15. The samples used were the powder-granule combination preparations in 5 grades of powder/granule ratio ranging from 1/8 to 8/ 1, containing 1 powder and 1 of 4 granules of different physical properties as component.
As a result, the two-step dividing method did not show smaller variation of powder content than one-step dividing method, and it is complicated and requires much time. It is, therefore, concluded that the one-step dividing method is more adequate for division of powder-granule combination preparations so far as the automatic dividing and packing machine, such as L-2, equipped with the feeder that has the function of alternating motion, is used.

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The adsorption behavior of chlorhexidine gluconate (CHG) to absorbent cotton and gauze was investigated in order to elucidate the lowering of CHG concentration in aqueous solution immersed surgical cotton. CHG was scarcely adsorbed to plastic containers. The residual percentage of CHG in 0.02 and 0.05% CHG solutions containing 3% absorbent cotton fell in 2 days to 14 and 54%, respectively. In the case of 8% cotton, the residual percentage in the same solutions fell to 14 and 39%. Although the residual percentage differed with CHG concentration or quantities of cotton, the adsorption isotherms uniformly showed Langmuir type, and the amount adsorbed was about 9 mg/ g of absorbent cotton at the equilibrium concentration of more than 0.05%, as compared with 3 mg/ g in the case of gauze. Though the amount adsorbed was small, as indicated above, the effect of adsorption on bactericidal activity is not neigligible in view of the low CHG concentration used in hospitals. It is, therefore, desired that the amount of adsorption is taken into consideration when the CHG solutions are prepared.

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Compatibilities of Gastropylore (GSP), an extract from lamb's gastric mucosa, with antacids were studied in terms of the macroscopic changes and the residual protease activity. Magnesium oxide and sodium bicarbonate were selected as the antacids since these were frequently used concomitantly with GSP in clinical application. The admixtures of GSP with these antacids were wrapped with polyethylene-laminated glassine paper, polyethylene-laminated cellophane or high density polyethylene, and stored under various conditions as follows: relative humidity of 92% at 30°, 75% at 20°, and 52% at 5°, respectively.
As the result of the experiments, the residual protease activity of GSP under the severecondition (relative humidity of 92% at 30°) was stable for 2 weeks. GSP-sodium oxide admixture also showed distinct changes neither in the macroscopic observation nor in the residual protease activity under the relative hnmidity of 75% at 20° for two weeks. In GSP-sodium bicarbonate admixture, the residual protease activity becomes stable; however, the residual protease activity can be fairly meintained by using low humidity permeable film (high density polyethylene) as wrappings.

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Details of inquiries on the suspected contents of the prescriptions were studied from February to April 1980 and from July to September 1981 at 4 university hospital pharmacies. By plotting a x-R control chart of the number of inquiries in each pharmacy, the changes of mean value and variance of the number could be checked quickly. This made possible to take a suitable and immediate action to these changes. Classified by department of consultation, the inquiries received at the internal department gave 40 to 50% of the total inquiries. Furthermore, the inquiries of drugs were about 60% in one pharmacy while the inquiries on amounts of drugs were about 50% in the other pharmacies. This implies that pertinent drug information on the inquiries in each pharmacy should be provided to physicians, primarily to internists.

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In the process of preparing for the revision of the hospital formulary, we investigated into hospital formularies used at 150 hospitals in Japan. It was found that 75.2% of the hospitals surveyed hold their own formularies; most formularies appear in A6 format, and the information contained is given in tables. The formularies are mostly issued within 1 year after initiation of their preparation. They contain 291 pages on the average. Further, 93% of doctors used formularies, and 48.5% of them reported that they are satisfied with the given formularies, while 37.6 % asked for more details. Most doctors required more information, especially on “Precautions for Use.”
Many hospitals pointed out such problems in editing the hospital formularies as establishing the standard for summarizing information and for the expressions, and delaying work of procedures of preparation of revised package insert. The details of the investigation were analyzed also by the ownership and size of hospitals.

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