关键词: HY11018, 高效液相色谱-串联质谱, Beagle犬, 血药浓度, 抗心律失常化合物

Abstract: AIM: To establish a high performance liquid chromatography coupled with electrospray ionization mass/mass spectrometry( LC-MS/MS) method for determination of 1-(2,3-dihydro-6-propoxychromen-4-ylideneamino)-3-(3-(4-methylpiperazin-1-yl)propyl)imidazolidine-2,4-dione (to call “HY11018”) and investigate its pharmacokinetic and absolute bioavailability in Beagle dogs. METHODS: Eight Beagle dogs were given HY11018 of normal saline solution via i.g. and i.v. gtt by crossover design with the dose of 14.8 mg/kg. LC-MS/MS was used to determine plasma concentration of HY11018 . The pharmacokinetic pagameters was calculated by DAS2.1 and the absolute bioavailability was computed with AUC_(0-t). RESULTS: The method was linear over the range of 8—8000 μg/L (r=0.9995); the lower limit of quantitation (LLOQ) was evaluated to 8 μg/L; the extraction recovery of HY11018 in Beagle dog plasma was more than 90%; intra- and inter-batch precision expressed as RSD was less than 15%. All results accorded with FDA criteria for bio-sample analysis. After i.g. and i.v. gtt administration of 14.8 mg/kg HY11018, physiological disposition of the drug corresponded to two and three compartment models respectively. The absolute bioavailability was 70.5%. CONCLUSION: The convenient sensitive and specific methoddescribed in this study was applied well to the pharmacokinetics of HY11018 in Beagle dogs. HY11018 was quickly absorbed with high absolute bioavailability. The characteristic of physiological disposition of HY11018 can be describe as the “drug like” property, accordingly, it may be a new drug that can be developed.

Key words: HY11018, LC-MS/MS, Beagle dog, Drug plasm concentration, Antiarrhythmic agent