采用超高效液相色谱-串联质谱技术研究桔霉素在SD大鼠血浆中的动力学规律  

Kinetics of Citrinin in SD Rat Plasma by the Development of Ultra-high Performance Liquid Chromatography-Tandem Mass Spectrometry

作　　者：马泽锋 刘明慧 张志岐 韩铮[2] 聂冬霞 MA Zefeng;LIU Minghui;ZHANG Zhiqi;HAN Zheng;NIE Dongxia(School of Health Science and Engineering,University of Shanghai for Science and Technology,Shanghai 200093,China;The Institute of Agro-food Standards and Testing Technology,Shanghai Academy of Agriculture Sciences,Shanghai 201403,China)

机构地区：[1]上海理工大学健康科学与工程学院,上海200093 [2]上海市农业科学院农产品质量标准与检测技术研究所,上海201403

出　　处：《工业微生物》2024年第5期159-165,共7页Industrial Microbiology

基　　金：国家自然科学基金(31972178)。

摘　　要：文章旨在建立一种超高效液相色谱串联质谱(UHPLC-MS/MS)法用于检测SD大鼠血浆中的桔霉素(CIT),并计算其毒代动力学参数。经验证,该方法的CIT在0.2~200μg/L质量浓度范围内,具有良好的线性关系(R^(2)=0.9996),灵敏度高(检出限为0.1μg/L,定量限为0.2μg/L);在4个不同添加水平下,回收率为88.93%~107.38%,日内精密度和日间精密度分别为1.77%~3.62%和3.14%~6.95%,稳定性为2.12%~7.91%。研究将CIT以1.125 mg/(kg·bw)的剂量灌胃大鼠(n=5),并运用建立的UHPLC-MS/MS法检测不同时间点上大鼠血浆中的CIT质量浓度,以揭示其在大鼠体内的动力学规律。研究结果表明,给药后,在0~2 h内,CIT的质量浓度逐渐上升,并在2 h达到最大值,最大质量浓度为4078.37μg/L,随后质量浓度逐渐下降,并在72 h后血浆中的CIT质量浓度低于方法定量限。动力学参数计算结果显示,SD大鼠血浆中CIT的半衰期为45.59 h;消除速率为0.053 L/(kg·h);药时曲线下面积为21289.96μg·h/L;表观分布容积为0.194 L/kg。研究结果为阐明CIT的毒代动力学特征提供了重要依据,有助于完善CIT的风险评估数据。The article aimed to establish a ultra-high performance liquid chromatography-tandem mass spectrometry(UHPLC-MS/MS)to detect the citrinin(CIT)in the plasma of SD rats,and to calculate the toxicokinetic parameters.After validation,the CIT under this method was in the concentration range of 0.2-200μg/L,with the nice liner relationship(R^(2)=0.9996)and high sensitivity(limit of detection,0.1μg/L;limit of quantification,0.2μg/L).With four different spiked concentrations,the recoveries were in the range of 88.93%-107.38%,the intra-day and inter-day precisions were 1.77%-3.62%and 3.14%-6.95%respectively,and the stability was 2.12%-7.91%.Through administering CIT to rats(n=5)by gavage at a dose of 1.125 mg/(kg·bw),and using the aforementioned UHPLC-MS/MS,the concentrations of CIT in rat plasma at different time points were accurately determined to reveal the kinetics of CIT in rats.The results showed that after gastric gavage,the concentration level of CIT in the plasma gradually increased at 0-2 h,and reached its peak at 2 h with a maximum concentration of 4078.37μg/L.Subsequently,it gradually declined,and after 72 h,the CIT concentrations in the plasma were below the limit of quantification of the established method.Through the calculation of kinetic parameters,it was found that the half-life of CIT in SD rat plasma was 45.59 h,the elimination rate was 0.053 L/(kg·h),the area under the drug concentration-time curve was 21289.96μg·h/L,and the apparent volume of distribution was 0.194 L/kg.The research results can provide important basis for elucidating the kinetic characteristics of CIT,and be benificial for the improvement of the risk assessment data of CIT.

关 键 词：桔霉素 动力学 超高效液相色谱-串联质谱技术 大鼠 

分 类 号：R994.4[医药卫生—毒理学] O657.63[医药卫生—药学]