摘要
目的建立LCMS法测定犬血浆中盐酸伪麻黄碱浓度,以缓释成分盐酸伪麻黄碱为指标,观察犬单剂量ig西嗪伪麻缓释胶囊后血药浓度经时过程,估算相应的药代动力学参数。方法血浆中加入内标苯丙醇胺,碱化后用乙醚提取,采用选择性离子检测方法测定其血药浓度。色谱柱为ShimpackODS(50μm,250mm×20mmID),流动相为超纯水(内含02%醋酸+0005mmol/L醋酸铵溶液)乙腈(80∶20,v/v),流速02ml/min,柱温40℃。Beagle犬给药采用双交叉实验设计,剂量为120mg。结果盐酸伪麻黄碱线性范围0016～200μg/ml;最低检测浓度为0016μg/ml,方法回收率大于90%,日内日间变异均小于10%。Beagle犬单剂量ig西嗪伪麻缓释胶囊后,测得盐酸伪麻黄碱cmax为(071±016)μg/ml,tmax为(23±08)h,t1/2为(715±108)h,MRT为(1136±154)h,AUC0τ为(586±093)μg·h/ml。以扑尔伪麻片为对照,西嗪伪麻缓释胶囊相对生物利用度为(963±109)%,两制剂经方差分析显示tmax和cmax有显著差异。西嗪伪麻缓释胶囊具有一定的缓释特征。结论本方法专属性强,准确性好,可用于盐酸伪麻黄碱血药浓度测定和药代动力学研究。
AIM:To establish an LC-MS method for determination of pseudoephedrine in Beagle dog's plasma and to study its pharmacokinetics.METHOD:After alkalizing with a mixture of 1% NaOH 50 μl and 4% Na 2 CO 3 2.5 ml,the plasma samples,with the addition of phenylpropanolamine,were extracted with 4 ml ether.HPLC analysis was carried out through ODS C 18 Shim-pack column(5 μm,250 mm×2.0 mm).The mobile phase consisted of acetonitrile-0.2% acetic acid and 0.005 mmol/L ammionium acetate (20∶80,v/v) at a flow rate of 0.2 ml/min.The column temperature is 40 ℃.Analysis in the mass spectrometer was performed in the selected-ion monitoring model.Pseudoephedrine concentrations in plasma were determined and pharmacokinetic parameters were also estimated.RESULT:The standard curve was linear in the range of 0.016～2.00 μg/ml. Recoveries of pseudoephedrine at 0.062,0.25 and 2.0 μg/ml were 93.18%,99.40% and 96.90% respectively.The relative standard derivation of intra-day and inter-day was smaller than 10%.After ig a single dose,the pharmacokinetic parameters of pseudoephedrine were:c max 0.71±0.16 μg/ml,t max :2.3±0.8 h,t 1/2 :7.15±1.08 h,MRT:11.36±1.54 h,AUC 0-τ :5.86±0.93 μg·h/ml.CONCLUSION:The bioanalytical method of LC-MS is suitable for pharmacokinetics study of pseudoephedrine.
出处
《中国药科大学学报》
CAS
CSCD
北大核心
2004年第6期528-531,共4页
Journal of China Pharmaceutical University
基金
国家863计划资助项目(No2003AA2Z347A)
江苏省药物代谢动力学重点实验室资助项目(NoBM2001201)~~
