超高效液相色谱-三重四极杆/线性离子阱复合质谱法测定鸡蛋中黏菌素残留的研究

建立了鸡蛋中黏菌素残留检测的超高效液相色谱-三重四极杆/线性离子阱复合质谱方法（UPLC -QTRAP）。样品用25%甲醇提取后,正己烷去脂,固相萃取柱净化,上机测试。液相色谱条件：色谱柱为BEH C18（50 mm×2.1 mm,1.7 μm）,流动相为0.5%甲酸水溶液+0.5%甲酸乙腈溶液,梯度洗脱,流速为0.4 mL/min,柱温为30 ℃,进样量为5 μL。质谱条件：电喷雾正离子源（ESI+）,采用多反应监测-信息依赖扫描-增强子离子扫描（MRM-IDA-EPI）方式采集。结果表明：在鸡蛋中,黏菌素A和黏菌素B在20~800 ng/kg基质匹配标准溶液浓度范围内均呈现良好的线性关系,相关系数（R2）大于0.990;鸡蛋中黏菌素A和黏菌素B的定量限均为30 μg/kg,检测限为10 μg/kg。鸡蛋中黏菌素A和黏菌素B在30、150和300 μg/kg三个添加浓度平均回收率都在67.2％~106％之间,批内、批间RSD均小于20%。该方法定性准确、灵敏度高、简便快捷,回收率和精密度满足残留检测要求。     

氟苯尼考与黏菌素联用对猪大肠杆菌与链球菌的体外抗菌作用

采用棋盘法,测定了氟苯尼考与黏菌素联用对猪大肠杆菌、链球菌分离株的体外抗菌活性。结果表明:猪大肠杆菌、链球菌分离株均对氟苯尼考呈现出耐药性,其最小抑菌浓度(MIC)为0.64~5.12 mg/L,大部分大肠杆菌分离株对黏菌素耐药,仅对其中一株有明显效果。棋盘法测得氟苯尼考与黏菌素联合对猪大肠杆菌、猪链球菌分离株的部分抑菌浓度(FIC)指数为0.031 26~0.140 63,均为协同作用。当浓度大于或等于0.16 mg/L时即呈现出协同作用。     

Determination of a dosage regimen of colistin by pharmacokinetic/pharmacodynamic integration and modeling for treatment of G.I.T. disease in pigs

Colistin is an antimicrobial drug of the polymyxin group and COLIVET SOLUTION is an aqueous solution containing colistin sulphate (2 × 10⁶ IU/mL), formulated for oral administration. The target species is the pig, particularly the suckling and post weaning animal. This investigation was undertaken to provide pharmacokinetic and pharmacodynamic data on which to base the selection of dosage rate and interval of the solution for the treatment of porcine colibacillosis.Colistin absorption from the gastrointestinal tract of young pigs, when administered at dosage rates of 25,000, 50,000 and 1,00,000 IU/kg, was slight or absent. The drug was therefore restricted almost entirely to the required site of action. The colistin concentration-time profile within the jejunum and ileum was established, and this enabled determination of the pharmacokinetic variables, maximum concentration (C_max) and area under curve (AUC) and derivation of the surrogate indices of antibacterial activity, C_max/minimum inhibitory concentration (MIC) and AUC/MIC through integration of in vivo data with the results of in vitro potency studies for four strains of Escherichia coli.In the in vitro bacterial growth inhibition studies colistin acted by a concentration-dependent killing mechanism. Numerical values for the surrogate parameter AUC/MIC producing bactericidal and eradication effects of colistin against four strains of E. coli were established by PK-PD modeling based on the sigmoidal E_max equation. These data were used to predict a daily dosage regimen for colistin.