胍丁胺的衍生化GC-NPD测定及大鼠药动学研究

Derivative GC-NPD Determination of Agmatine and Its Pharmacokinetics Study in Rat

关键词:  胍丁胺  衍生化  气相色谱法  药代动力学

Key words:  agamatine  derivative  GC  pharmacokinetics

摘要:

目的 建立衍生化气相色谱法测定大鼠血浆中胍丁胺浓度方法并研究其在大鼠体内的药动学。方法 应用六氟乙酰丙酮(HFAA)衍生化气相色谱氮磷检测器(GC-NPD)分析血浆样品中的胍丁胺浓度。结果 胍丁胺在大鼠血浆中的线性范围为0.1～50 μg·mL^-1 , 最低检测浓度为0.1 μg·mL^-1。高、中、低三种浓度的平均方法回收率分别为87.7%，90.7%，101%。日内、日间精密度(RSD)均小于12%。大鼠灌胃胍丁胺符合二室模型，t1/2为109 min，tmax为26 min，Cmax为1.91 μg·mL^-1，AUC_0-300 min为145 μg·min·mL^-1。结论 本方法稳定、可靠，可用于胍丁胺的血药浓度分析及大鼠灌胃药代动力学研究。

Abstract:

OBJECTIVE To develop a derivative GC-NPD method for the determination of agmatine in rat plasma and to study its pharmacokinetics in rats. METHODS GC-NPD analysis method was used to determine agmatine in rat plasma after derivative with HFAA. RESULTS The calibration curve of agmatine in rat plasma was linear (r=0.998 0) in the range of 0.1- 50 μg·mL^-1. The lowest detectable concentration was 0.1 μg·mL^-1. The recoveries at the concentration of 0.2, 2 and 5 μg·mL^-1 were 87.7%, 90.7%, 101%, respectively. The inter- and intra-day RSDs were all less than 12%. Pharmacokinetics parameters of agmatine in rats after i.g were fit to the two-comparment model. Fitting with the two-comparment model, the pharmacokinetics parameters of agmatine in rats after ig showed that the half-life of agmatine was 109 minutes, tmax was 26 min, Cmax was 1.91 μg·mL^-1, and AUC_0-300 min was 145 μg·min·mL^-1, respectively. CONCLUSION This method is proved to be precise and reliable enough to be applied to the pharmacokinetics studies of agmatine in rats via i.g.