中文摘要：

目的：采用液相色谱-质谱联用分析方法研究盐酸关附甲素在Beagle犬体内的吸收特性。方法：6只Beagle犬采用双交叉实验设计,空腹单次静脉或灌胃给予盐酸关附甲素（4mg/kg）,采集不同时间点的血样,采用LC-MS法进行血浆药物浓度测定,求算相应的药代动力学参数。结果：6只Beagle犬灌胃4mg/kg盐酸关附甲素后体内过程符合二房室模型,实测的血浆药物浓度曲线下面积AUC0-48h为（18429±7281）ng·mL-1·h,最大血浆药物浓度Cmax为（1988±972）ng/mL,达峰时间tmax为（0.8±0.7）h,末端相消除半衰期t1/2为（11.2±1.6）h。与静脉注射给药相比其绝对生物利用度F为（99.0±11.2）%,拟合求得的吸收速率常数（K01）为（7.563±4.612）/h。结论：盐酸关附甲素在Bea-gle犬体内吸收迅速且完全,临床上可考虑采用口服剂型代替注射剂以便于病人用药。

英文摘要：

AIM： An LC-MS method was developed and validated for the analysis of Guanfu Base A in dog plasma to support the pharmacokinetic study.METHODS： Blood was withdrawn at different times and absolute bioavailability was studied by LC-MS at dosage of 4 mg/kg in 6 beagle dogs.RESULTS：The pharmacokinetic of Guanfu Base A in Beagle dogs fits best to two compartment model with AUC0-48 h,Cmax,tmax and half life t1/2 of（17623.9±7006.4） ng·mL-1·h,（1988±972）ng/mL,（0.8±0.7） h,and（11.2±1.6） h,respectively.Compared with i.v administration,the absolute bioavailability of Guanfu Base A was（99.0±11.2）%,with absorption rate（K01）at（7.563±4.612）/h.CONCLUSION： After oral administration,GFA can be rapidly and completely absorbed by Beagle dogs,which suggested that oral administration of Guanfu Base A could be a substitute way for anti-arrhythmic treatment.