1987 Volume 2 Issue 2 Pages 113-121
A GC/MS method for the determination of CS-570, a chemically stable prostacyclin analogue, was developed. This assay method was applied to study a disposition of CS-570 in dogs after a single or continuous intravenous administration. An acidified plasma, obtained from dogs, was spiked with 2H6-CS-570 as an internal standard and extracted with reversed-phase (ODS) cartridges. After methylation with diazomethane, further purification was carried out using normal-phase (Si) cartridges. The methyl-dimethyl-iso-propylsilyl derivative of CS-570 exhibits some suitable properties in GC/MS analysis showing the intense peak at m/z (M-43) by electron ionization. At the concentration of 8 and 80 ng/ml in plasma, CV% were 2.8 and 1.7 respectively. The limit of determination is 1 ng/ml when 1 ml sample is available. Dogs were received i. v. injection of CS-570 at a single dose of 100 μg/kg or i. v. infusion at the rate of 256 and 512 ng/kg/min for 60 min. A steep and biphasic decline of CS-570 concentration in plasma was observed both after rapid injection and after the end of the infusion with half-life of approximately 10 min at β-phase. During the continuous infusion, a rapid increace of CS-570 concentration in plasma was observed and it reached 95 % of the steady-state level within 15 min. Linear relationship was obtained between doses and AUC. A metabolite, β-oxidation product, was also found in dog plasma.
