Junko Kizu

Determination of theophylline and its metabolites in biological samples by liquid chromatography-mass spectrometry

Liquid chromatography-mass spectrometry (LC-MS) is a powerful tool for analysis of drugs and their metabolites. We used a column-switching system in combination with atmospheric pressure chemical ionization LC-MS (LC-APCI-MS) for the determination of theophylline and its metabolites in biological samples. The separation was carried out on a reversed-phase column using methanol-20 mM ammonium acetate as a mobile phase at a flow-rate of 1 ml/min in 30 min. In the mass spectrum, the molecular ions of these drugs and metabolites were clearly observed as base peaks. This method is sufficiently sensitive and accurate for the pharmacokinetic studies of these drugs.

Development and clinical application of high performance liquid chromatography for the simultaneous determination of plasma levels of theophylline and its metabolites without interference from caffeine

A high performance liquid chromatography (HPLC) method has been developed for the simultaneous determination of plasma levels of theophylline and its metabolites without interference from caffeine or caffeine metabolites. The method is simple and of practical use because it is applicable even to plasma samples from patients who take caffeine-containing beverages. The method was also reproducible with a coefficient of variation of less than 5% for each analyte. The levels of theophylline, determined by HPLC, were validated by their high correlation to the levels obtained by fluorescence polarization immunoassay. HPLC was used to determine theophylline levels in patients with bronchial asthma. The data revealed that the ratio of 1,3-dimethyluric acid, the major metabolite of theophylline, to theophylline concentration in the plasma was within a narrow range in most patients (0.055 +/- 0.01, n = 66), regardless of the method of theophylline administration or the time of blood sampling. Conversely, this ratio was as low as 0.027 +/- 0.005 in the patient with a long plasma half-life of theophylline. These results suggest that it may be possible to predict the plasma half-life of theophylline for each patient from a single blood sample. This may be useful when planning theophylline administration, especially in patients with abnormal theophylline metabolism.

Topical Application of a Novel, Water-soluble γ-Tocopherol Derivative Prevents UV-induced Skin Damage in Mice¶

Abstract We investigated whether the topical application of a novel, water-soluble γ-tocopherol (γ-Toc) derivative, γ-tocopherol-N,N-dimethylglycinate hydrochloride (γ-TDMG), could protect against UV-induced skin damage in hairless mice. Topical pre- or post-application of a 5% (93 mM) γ-TDMG solution in water/propylene glycol/ethanol (2:1:2) significantly prevented sunburn cell formation, lipid peroxidation and edema/inflammation that were induced by exposure to a single dose of UV irradiation of 5 kJ/m2 (290–380 nm, maximum 312 nm). This effect was greater than that seen with two α-Toc derivatives, α-tocopherol acetate (α-TA) and α-tocopherol-N,N-dimethylglycinate (α-TDMG). When a 5% solution of γ-TDMG was applied to mouse skin for 1 h, cutaneous γ-Toc increased by 25-fold after 24 h; levels of cutaneous α-Toc increased by only two- and eight-fold in α-TDMG and α-TA treated skins, respectively. These findings indicated that γ-TDMG immediately converted to γ-Toc in the skin and suggest that ability of γ-TDMG to protect the skin from the damaging effects of irradiation was due to its conversion to γ-Toc. When a 5% solution of γ-Toc was applied to mouse skin for 1 h, cutaneous γ-Toc rapidly increased by 25-fold, but fell to baseline levels by 24 h. In contrast, the concentration of γ-Toc in skin that was treated with γ-TDMG similarly increased, but these high levels were maintained after 24 h. These results suggest that γ-TDMG may be a more effective source of γ-Toc in skin. Thus, the topical application of γ-TDMG may be efficacious for the prevention of UV-B-induced skin damage.

Enhanced theophylline metabolism in patients with bronchial asthma at age 4 and under

The plasma levels of theophylline (TP) and its metabolites were measured in patients with bronchial asthma who were treated with a slow-release preparation of TP. The ratios of the plasma levels of these metabolites to TP levels in the group aged 1-4 years were larger than those in the group aged 5 years and older, suggesting enhanced activity of drug-metabolizing enzymes during infancy.

Sensory Evaluation of Practicableness of Powder Preparations for Dispensing (1)

There are many factors affecting practicableness of powder preparations for dispensing, such as angle of repose, angle of spatula, compressibility, flocculation, uniformity, particle diameter, specific gravity and porosity. In this study, the practicableness of powders for dividing with Konishis automatic powder divider or pile packer and for weighing was examined by sensory evaluation. It was found out that there is a significant relationship between practicableness for dispensing and the factors above mentioned. The practicableness was also studied in terms of the powder fluidity index of Ralph L. Carr. Dividing and folding services have become convenient with an introduction of imporved automatic dividers or change of dosage form from powder to granules or fine granules. But there are some problems in dispensing granules and fine granules. Fluidity and other properties concern directly not only with the practicableness for weighing but with mixing and dividing errors and practicablen