| New HPLC-UV methods for the determination of CS-940 and KNT-009 in biological specimen were developed and successfully used in the preclinical metabolism and pharmacokinetics study of these two new quinolones.1. Development of the method for the determination of CS-940 in biological specimenA rapid, sensitive HPLC-UV method was developed to determine CS-940 in biological specimen. After liquid-liquid extraction, samples were separated on a C18 column. Acetylaminobenzene was used as the internal standard and the mobile phase consisted of acetonitrile: 50 mmol·l-1 NH4H2PO4 (pH 2.5): tetrahydrofuran (20: 80: 0.8, v/v/v). The wavelength of UV was 295 nm. The linear calibration curve was obtained in the range of 0.100-50.00 μg·ml-1 in rat plasma, and 0.050-25.00 μg·ml-1 in dog plasma and tissue homogenate.2. Preclinical metabolism and pharmacokinetics study of CS-940 Preclinical metabolism and pharmacokinetics of CS-940 was systematicallystudied by the developed HPLC-UV method.Investigation of absorptionFollowing a single i.v. administration of CS-940 to rats and dogs in three doses, respectively, plasma concentrations of CS-940 were determined. The pharmacokintic parameters were calculated by non-compartmental method using Topfit 2.0. AUC0-t, AUC0∞ increased in a dose-proportional manner over this dose range. The pharmacokinetic behaviors of CS-940 in rats and dogs were all fitted to two-compartmental models.Investigation of plasma protein bindingAt the rat plasma concentrations of 0.400, 2.00, 10.00 and 50.00 μg·ml-1, plasma protein binding of CS-940 were 28.75±3.36, 31.81±2.77, 32.31±2.09 and 24.90±3.55%, respectively.
|
PDF Full Text Request