摘要
目的:建立快速灵敏的气质联用(GC-MS)法测定莪术中β-榄香烯在大鼠血浆中血药浓度,并研究β-榄香烯在大鼠体内的药代动力学特征。方法:血浆样品的处理采用正己烷液-液萃取方法,萘为内标。色谱柱:DB-5毛细管柱(30 m×0.25 mm,0.25μm);程序升温:初始60℃,保持1 min,再以30℃·min^(-1)的速度升温至160℃,保持3 min,再以10℃·min^(-1)的速度升温至200℃,保持2 min。采用电子轰击离子源及选择离子扫描模式(SIM);选择监测离子:β-榄香烯m/z 93,内标m/z 128。按β-榄香烯10 mg·kg^(-1)灌胃给药后,测定大鼠血浆中β-榄香烯的浓度,并用DAS 2.0软件计算药代动力学参数。结果:血浆中β-榄香烯质量浓度在0.05～200.0μg·mL^(-1)浓度范围内线性关系良好(r^2=0.999 1),定量下限为0.05μg·mL^(-1);低、中、高3个浓度准确度、日内及日间精密度均小于5%;提取回收率分别为91.7%、105.1%、108.8%;低、中、高3个浓度血浆样品在室温放置12 h,4℃冰箱中放置24 h及反复冻融4次后均能保持稳定。大鼠灌胃莪术提取液后β-榄香烯药-时曲线符合二室模型;主要药代学参数:AUC_(0-t)为(9.83±1.07)μg·L^(-1)·h,t_(1/2α)为(0.47±0.05)h,t_(1/2β)为(1.82±3.11)h,T_(max)为(2.06±0.37)h,C_(max)为(2.61±0.17)μg·mL^(-1)。结论:该方法简便、准确,专属性强,适用于莪术中β-榄香烯在大鼠体内的药代动力学研究。
Objective:To establish a rapid,sensitive method for the determination of plasma concentration ofβ-elemene in Curcuma zedoaria using capillary gas chromatography coupled to mass spectrometry(GC-MS) and to study the pharmacokinetics in rats.Methods:The plasma sample was treated with a liquid-liquid extraction method of n-hexane,and naphthalene was used as an internal standard(IS).The determination was performed on DB-5 column(30 m×0.25 mm,0.25 μm).The initial column temperature was 60 ℃,maintained for 1 min,then raised to 160 ℃ at a rate of 30 ℃·min^-1,maintained for 3 min,and finally increased to 200 ℃ at a rate of 10 ℃·min^-1 and maintained for 2 min.EI and single ion monitoring pattern(SIM)were used for ion scanning with m/z 93(β-elemene) and m/z 128(IS).After administration of β-elemene 10 mg·kg^-1 by oral gavage,the concentration of β-elemene in rat plasma was determined,and the pharmacokinetic parameters were calculated by DAS 2.0 software.Results:There was excellent linearity of the plasma concentration of β-elemene in the range of 0.05-200.0 μg·mL^-1(r2=0.999 1),and the lowest limit of quantification was 0.05 μg·mL^-1.The accuracy,intraday and inter-day precisions of low,medium and high concentrations were less than 5% and the recovery rates were 91.7%,105.1% and 108.8%,respectively.The plasma samples of low,medium and high concentrations were kept at room temperature for 12 h,and were stable after being placed in refrigerator at 4 ℃ for 24 h and repeatedly frozen and thawed for 4 times.The concentration-time curve of β-elemene of the extract of rats after administration of Curcuma zedoaria by oral gavage was consistent with the two-compartment model.The main pharmacokinetic parameters were as follows:AUC0-t was(9.83±1.07)μg·L^-1·h,t1/2α was(0.47±0.05)h,t1/2β wss(1.82±3.11)h,Tmax was(2.06±0.37)h,and Cmax was(2.61±0.17)μg·mL^-1.Conclusion:The established method is simple,accurate,specific and suitable for pharmacokinetic studies of β-elemene in curcuma zedoaria in rats.
作者
李婧
刘文静
LI Jing;LIU Wen-jing(College of Pharmacy,Southwest Minzu University,Chengdu 610041,China)
出处
《药物分析杂志》
CAS
CSCD
北大核心
2019年第5期846-851,共6页
Chinese Journal of Pharmaceutical Analysis
基金
西南民族大学中央高校基本科研业务费专项资金项目(No.2019NQN56)
