摘要
目的建立测定大鼠血浆中卡博替尼浓度的高效液相色谱-串联质谱(HPLC-MS/MS)方法,并用于其混悬剂的药动学研究。方法用蛋白沉淀法处理大鼠血浆,采用AB SCIEX 4500液相色谱质谱联用系统测定血浆中卡博替尼浓度。色谱柱:Agilent Eclipse Plus C_(18),流动相A:水(含0.1%甲酸),流动相B:乙腈(含0.1%甲酸),梯度洗脱。电喷雾离子源,正离子模式,多反应监测(MRM)模式,监测离子:m/z502.3/391.3。结果卡博替尼血药浓度线性范围为2.5~500 ng/ml(R^(2)=0.9987),定量限为2.5 ng/ml,批内和批间精密度试验RSD≤9.6%,方法回收率为99.2%~103.9%。雌性、雄性SD大鼠灌胃给予1 mg/kg卡博替尼混悬剂后,C_(max)和AUC_(0-t)分别为138.7 ng/ml和2850.4 ng·h/ml,122.7 ng/ml和2875.7 ng·h/ml。结论方法灵敏度高、处理及检测过程简单快速,适用于大鼠血浆中卡博替尼的浓度测定及其混悬液的药动学研究。
Objective To establish an HPLC-MS/MS method for the determination of cabozantinib in rat plasma and apply it in pharmacokinetic study of its suspension.Methods Following protein precipitation,the concentration of cabozantinib in rat plasma was measured by AB SCIEX 4500 liquid chromatography-mass spectrometry system.The separation was performed on an Agilent Eclipse Plus C_(18) column.Acetonitrile-water containing 0.1%formic acid were used as the mobile phase for gradient elution.Electrospray ionization source in positive ion mode was adopted,and multiple reaction monitoring(MRM)mode was used for detection,with m/z 502.3/391.3 as monitoring ion pair.Results The calibration curve of cabozantinib presented a good linear relationship in the range of 2.5-500 ng/ml(R^(2)=0.9987).The lower limit of quantification was 2.5 ng/ml.RSDs of the intra-batch and inter-batch precision tests were not more than 9.6%.The recovery was within the range of 99.2%-103.9%.In female and male rats after intragastric administration of 1 mg/kg cabozantinib suspension,the C_(max) and AUC_(0-t) were 138.7 ng/ml and 2850.4 ng·h/ml,and 122.7 ng/ml and 2875.7 ng·h/ml,respectively.Conclusion The method is sensitive,simple and rapid,and is suitable for the determination of cabozantinib in rat plasma and the pharmacokinetics study of its suspension.
作者
王芳
徐玲玲
刘小雨
李晓萌
雷振宇
戚敏
陈凯
WANG Fang;XU Ling-ling;LIU Xiao-yu;LI Xiao-meng;LEI Zhen-yu;QI Min;CHEN Kai(Shandong Innovation Center of Engineered Bacteriophage Therapeutics,Shandong Academy of Pharmaceutical Sciences,Jinan 250101,China)
出处
《食品与药品》
2025年第4期358-362,共5页
Food and Drug
