Self-reversal phenomena of toroidal current by reversing the external toroidal field in helicity-driven toroidal plasmas.

In order to understand self-organization in helicity-driven systems, we have investigated the dynamics of low-aspect-ratio toroidal plasmas by decreasing the external toroidal field and reversing its sign in time. Consequently, we have discovered that the helicity-driven toroidal plasma relaxes towards the flipped state. Surprisingly, it has been observed that not only toroidal flux but also poloidal flux reverses sign spontaneously during the relaxation process. The self-reversal of the magnetic fields is attributed to the nonlinear growth of the n=1 kink instability of the central open flux.

Stereoselective determination of a new antidepressant, E2011, and its diastereoisomer as a metabolite by high-performance liquid chromatography.

A stereoselective HPLC method has been developed for the determination of E2011 (compound I) and one of its metabolites and diastereoisomers, ER-20593 (compound II), in plasma. The two substances and the internal standard were extracted from plasma, followed by two purification steps. In the first step, a minicolumn, Bond Elut C18, was used and in the second step, another minicolumn, Bond Elut Si, was used for purification of the compounds. After the purification, the compounds were analyzed by HPLC with two Chiralpak AD columns. In this procedure, compounds I and II were stable and there was no chiral inversion. The within-day and the between-day assays were performed in rat plasma, where compounds I and II existed simultaneously. The within-day and the between-day precisions of compound I were 2.0 approximately 10.1% and 1.3 approximately 7.1%, and the within-day and the between-day accuracies were -8.2 approximately +3.0% and -6.6 approximately +4.0% in the concentration range 0.003-10 microg ml(-1). The within-day and the between-day precisions of compound II were 1.7 approximately 16.9% and 0.9 approximately 4.5% and the within-day and the between-day accuracies were -9.0 approximately +2.4% and -5.6 approximately +3.8% in the concentration range of 0.005-0.5 microg ml(-1). QC samples for compound I and II were stable for at least 3 months. The method was applied to measure the levels of compound I and II in the rat plasma after oral administration of compound I.

Development of radioimmunoassay for the novel platelet activating factor receptor antagonist, E6123, and its application to pharmacokinetics in laboratory animals.

A direct radioimmunoassay for the determination of E6123, a novel antagonist of platelet activating factor (PAF) receptor, was developed in order to study the pharmacokinetics at low dose. This procedure used [3H]E6123 as the radioligand and an antiserum obtained from rabbits immunized with the hapten covalently bound to bovine serum albumin. M1B, one of the main metabolites of E6123, exhibited cross-reactivity with antisera. But this metabolite had no effect on measurements of E6123, because the amount of M1B in plasma radioactivity after administration of [14C]E6123 to dogs and monkeys was low. The sensitivity limit of this assay was 25 pg/ml of plasma when 0.1 ml of plasma was used and the assay showed good accuracy and high precision. The validity of the radioimmunoassay was demonstrated by comparative analysis of a number of samples after oral and intravenous administration (1.0 mg/kg) by HPLC-UV method (r = 0.972-0.984, slope = 1.0314-1.2143). The pharmacokinetics of E6123 was studied at a dose of 30 micrograms/kg. After intravenous administration, the plasma concentration-time curves in all species fitted a two-compartment model and the terminal half-lives in guinea pigs, dogs and monkeys (both poor and extensive metabolizers) were 4.77, 1.71, 5.34 and 1.07 h, respectively. After oral administration, the maximum plasma concentrations were obtained within 0.83-3.00 h and the half-life for each animal was almost the same as that after intravenous administration. The mean bioavailabilities of E6123 in guinea pigs, dogs and monkeys (poor and extensive metabolizers) were 106.9, 45.7, 59.1 and 22.8%, respectively.