摘要
目的建立灵敏、稳定的头孢曲松肉汤浓度的高效液相色谱分析方法,评价中空纤维感染模型中头孢曲松的药动学特征,为优化临床给药方案和延缓耐药性发展提供研究基础。方法以甲硝唑为内标,肉汤样品经甲醇沉淀蛋白、浓缩后,采用ZORBAX Eclipse Plus C_(18)色谱柱(4.6 mm×150 mm,5μm)分离,以0.05 mol/L KH_(2)PO_(4)水溶液(K_(2)HPO_(4)调节pH值至7.0)-甲醇(91:9)为流动相,流速1 mL/min,检测波长254 nm,柱温36℃,进样量20μL。建立中空纤维感染模型,模拟头孢曲松临床多次给药方案(1.5 g,静脉滴注1 h,1次/12 h,疗程7 d),计算药动学参数。结果头孢曲松在4.994~249.7μg/mL内线性关系良好(r≥0.998);批内和批间精密度均小于13.9%,准确度为94.3%~108.1%;提取回收率在74.7%~89.4%之间;稳定性良好。中空纤维感染模型中头孢曲松药动学参数为C_(max)=152.2μg/mL,T_(max)=1 h,t_(1/2)=8.70 h,AUC_(0-36)=1231μg/mL·h,AUC_(0-∞)=1286μg/mL·h,与药品说明书和相关文献数据基本一致。结论所建立的高效液相色谱法,专属性强、重现性好、灵敏度高,适用于中空纤维感染模型中头孢曲松的体外药代动力学研究。
Objective In this study,a sensitive and stable HPLC method for ceftriaxone broth concentration was established to investigate its pharmacokinetic characteristics in a hollow-fiber infection model,thus providing the research basis for optimizing clinical drug administration and delaying the development of drug resistance.Methods Using metronidazole as the internal standard,the broth samples were extracted with methanol and concentrated,and then separated on a ZORBAX Eclipse Plus C_(18) column(4.6 mm×150 mm,5μm).The mobile phase was 0.05 mol/L potassium dihydrogen phosphate aqueous solution-methanol(91:9),adjusted to pH 7.0 with dipotassium hydrogen phosphate,at a flow rate of 1 mL/min.The UV detection wavelength was 254 nm;the column temperature was 36℃;the sample size for quantification was 20μL.Ceftriaxone clinical multi-dose regimen(1.5 g,intravenous infusion for 1 h,once every 12 h,treatment course for 7 d)was simulated in a hollow-fiber infection model,and pharmacokinetic parameters were calculated.Results The method exhibited a good linearity over the ceftriaxone concentration range of 4.994~249.7μg/mL(r≥0.998).The values of intra-batch and inter-batch precision were all within 13.9%,and the accuracy was 94.3%~108.1%.Ceftriaxone was stable in common bacterial broth medium under different storage conditions,with extraction recovery ranged from 74.7%to 89.4%.The pharmacokinetic parameters of ceftriaxone in a hollow-fiber infection model were C_(max)=152.2μg/mL,T_(max)=1 h,t_(1/2)=8.70 h,AUC_(0-36)=1231μg/mL·h,AUC_(0-∞)=1286μg/mL·h,which were basically consistent with the drug instructions and related literature data.Conclusion The established HPLC method had excellent specificity,reproducibility,and sensitivity,and thus it was suitable for the in vitro pharmacokinetic study of ceftriaxone in a hollow-fiber infection model.
作者
陈美玲
何晓静
菅凌燕
李晓冰
Chen Mei-ling;He Xiao-jing;Jian Ling-yan;Li Xiao-bing(Department of Pharmacy,Shengjing Hospital of China Medical University,Shenyang 110004)
出处
《中国抗生素杂志》
CAS
CSCD
北大核心
2022年第12期1274-1279,共6页
Chinese Journal of Antibiotics
基金
国家临床药学重点专科建设项目(No.2013/2014)
中国医科大学附属盛京医院345人才工程计划。
