摘要
目的 :建立犬血浆中舒巴坦浓度的LC MS测定方法 ,对Beagle犬单用和与头孢他啶注射剂合用后舒巴坦血药浓度进行定量研究 ,考察头孢他啶对舒巴坦药代动力学行为的影响。方法 :血浆中加入内标地高辛 ,用乙腈沉淀蛋白 ,取上清液进行LC MS测定。色谱柱为Shim packODS 5 0 μm ,2 5 0mm× 2 0mmI.D .,流动相A :5 0 0ml水 +2 0 μl三乙胺 +0 6mg氯化铵 ,流动相B :甲醇。以 0 2ml/min的流速进行梯度洗脱 ;动物实验采用三交叉实验设计。结果 :舒巴坦线性范围为 0 31～ 80 0 0 μg/ml,最低检测浓度为 0 31μg/ml,方法回收率大于90 % ,日内日间变异系数低浓度小于 2 0 % ,中高浓度小于 15 %。应用本法测定 9条Beagle犬单用和与头孢他啶合用后舒巴坦的血药浓度经时过程 ,静脉注射 13mg/kg的舒巴坦与 2 6mg/kg头孢他啶合用后 ,估算的AUC3 60 、t1/ 2 ,Cl和Vd分别为 386 5 2 9± 1115 13μg·min/ml,5 7 72± 6 37min ,3 5 0± 0 85ml/min/kg和 0 2 9± 0 0 9l/kg ,与单用 13mg/kg舒巴坦的AUC3 60 36 6 9 89± 92 2 17μg·min/ml,t1/ 2 6 6 98± 11 0 7min ,Cl3 5 6± 0 75ml/min/kg和Vd0 34± 0 0 8l/kg相近。结论 :本方法可用于犬血浆中舒巴坦的浓度测定及其药代动力学研究。头孢他啶不影响舒巴?
AIM:To develop an LC-MS method to determine sulbactam concentration and to study pharmacokinetics of sulbactam when co-administrated with ceftazidime in Beagle dog. METHOD:After adding digoxin,the internal standard,the plasma samples were mixed 10 min with 1ml acetonitrile. After centrifuging,5 μl supernatant was injected into a C 18 Shim-pack 250 mm×2.0 mm I.D. column. Analysis was conducted at a flow rate of 0.2 ml/min by gradient elution The elute from the HPLC column was directly plumbed into ESI probe Analysis in the mass spectrometer was operated in the selected-ion monitoring model Sulbactam concentrations in plasma were determined and pharamcokinetic parameters were also estimated RESULT:The standard curve was linear in the range of 0 31～80 00 μg/ml with the correlation coefficient of 0 99(P<0 01) Recoveries of sulbactam at 0 62,5 00 and 80 00 μg/ml were 95 43,92 92 and 99 81% respectively After iv Beagle dogs 13 mg/kg sulbactam and 26 mg/kg ceftazidime,the pharmacokinetic parameters of sulbactam were:AUC 360 3865 29±1115 13 μg min/ml,t 1/2 57 72±6 37 min,Cl 3 50±0 85 ml/min/kg,V d 0 29±0 09 l/kg.After iv 13 mg/kg sulbactam,the parameters were:AUC 360 3669 89±922 17 μg·min/ml,t 1/2 66 98±11 07 min,,Cl 3 56±0 75 ml/min/kg,V d 0 34±0 08 l/kg Pharmacokinetic parameters of single sulbactam were similar to those when co-administrated with ceftazidime CONCLUSION:The bioanalytical method of LC-MS is suitable for pharmacokinetic study of sulbactam.There's no significant difference between sulbactam and sulbactam/ceftazidime for injection in pharmacokinetics of sulbactam
出处
《中国药科大学学报》
CAS
CSCD
北大核心
2004年第5期433-436,共4页
Journal of China Pharmaceutical University
基金
国家 8 63计划资助项目 (No 2 0 0 3AA2Z3 47A)
江苏省药物代谢动力学重点实验室资助项目(No BM2 0 0 12 0 1)~~
