摘要
抗心律失常新药关附甲素(Guan—fu base A)与三氟醋酐反应,迅速定量地生成双-三氟乙酸酯衍生物,其结构经GC-MSD的分析得到证实。关附甲素衍生物经气相色谱分离后,在电子捕获检测器上有较高的响应,线性范围宽(10～2.0×10~4ng/ml,r=0.9984)。血中平均回收率为97.52％。本法以烯丙洛尔(alprenolol)为内标,定量准确,日内及日间差的变异系数分别小于7％和9％,并已成功地用于关附甲素临床前的药代动力学研究。
Guan-fu base A, a new antiarrhythmic alkaloid with a structure ofC_(20)-diterpenoid, was first isolated from the tuber of Aconitum coreanum (Levl.)Raipaicsin China in 1966. An analytical method of GC-ECD has been established in this paperfor the determination of its concentration in rabbit plasma in order to study its pharmacokinetics in preclinical pharmacology. Guan-fu base A and the internal standardalprenlol (ALP)was found to react rapidly and quantitatively with trifluoroacetic anhydride(TFAA)to produce derivatives GFA-TFAA and ALP-TFAA which were identified byGC-MSD. An optimal GC-ECD system for the separation and determination of thederivatives following the sample preparation was established. There was a wide linear rangeof the method from 10～2×10~4ng/ml (r=0. 9984). The average recovery of Guan-fubase A from the spiked plasma was 97.52%. The coefficient of variation of between-dayand within-day were less than 9% and 7%, respectively. The method was used to determineGuan-fu base A in the plasma of 15 rabbits following intravenous administration of 3dosages of 0.4, 2 and 10 mg per kg of body weight.
出处
《药学学报》
CAS
CSCD
北大核心
1992年第7期533-538,共6页
Acta Pharmaceutica Sinica
