伊维菌素缓释注射液的制备工艺及在绵羊体内药代动力学研究  

Study on preparation and pharmacokinetics of Ivermectin Sustained-release Injections in sheep

作　　者：任丽君[1,2] 郭玉娟[2] 姚军[2] 李新霞[2] 陈坚[2] 

机构地区：[1]昌吉职业技术学院,昌吉831100 [2]新疆医科大学药学院,乌鲁木齐830054

出　　处：《西北药学杂志》2016年第5期497-500,共4页Northwest Pharmaceutical Journal

摘　　要：目的制备伊维菌素缓释注射液,采用HPLC法测定绵羊血浆中伊维菌素的质量浓度并进行药代动力学研究。方法 (1)以伊维菌素为原料,用质量分数为2%的硬脂酸铝蓖麻油作为溶剂,制备伊维菌素缓释注射液。(2)采用HPLC法检测血浆中伊维菌素的质量浓度。色谱柱:Zirchrom C18色谱柱(250mm×4.6mm,5μm);流动相:甲醇-水(92∶8);流速:1.0mL·min^(-1);柱温:40℃;检测波长:245nm;苏丹Ⅲ为内标。结果 (1)制备得到黄色、澄明油状的伊维菌素缓释注射液。(2)伊维菌素质量浓度在2.0~20.0和20.0~200.0ng·mL^(-1)范围内线性良好(r分别为0.997 7和0.999 3)。最低检测质量浓度为1.8ng·mL^(-1)。样品平均回收率为101.8%。日内、日间精密度的RSD值均小于5%。绵羊皮下注射伊维菌素10mg·kg^(-1)后,其主要药动学参数:t_(max)=8.0d,C_(max)=82.3ng·mL^(-1),AUC=3 642ng·d·mL^(-1),MRT=45.9d。结论 (1)采用生物体较难吸收的蓖麻油作为溶剂,可以起到长期缓释的目的,缓释作用达4个月。(2)HPLC法简单、准确、可靠,适用于伊维菌素的血药质量浓度分析及药代动力学研究。Objective To study the preparation process of Ivermectins（IVM）Sustained-release Injections,to develop an HPLC method for the determination of ivermectin concentration in sheep plasma,and to study its pharmacokinetics in sheep.Methods（1）Sustained-release Injections were prepared by using castor oil as the solvent.（2）The content of IVM in IVM Sustained-release Injections was determined by HPLC-UV.The plasma samples were extracted with ethyl acetate.The analysis involved a Zirchrom C18column（250mm×4.6mm,5μm）and methanol-water（92∶8）as mobile phase.The flow rate was 1.0mL·min^-1;the column temperature was 40 ℃,and the UV detection wavelength was 245 nm.Sudan Ⅲ was used as the internal standard.Results（1）IVM Sustained-release Injections were obtained.（2）The calibration curve was linear over the ranges of 2.0-20.0ng·mL^-1and20.0-200.0ng·mL^-1 with correlation coefficients of 0.997 7and 0.999 3;the limit of detection was 1.8ng·mL^-1;the mean recovery was 101.8%;the RSDs of intra-day and inter-day were less than 5%;the HPLC method of determination of ivermectin in plasma was established.After single dose of 10mg·kg^-1 in sheep,the main pharmacokinetics parameters were estimated to be as follows：tmax=8.0d,Cmax=82.3ng·mL^-1,AUC= 3 642ng·d·mL^-1,MRT=45.9d.Conclusion（1）By using the more difficult absorb solvent,castor oil,a long-term sustained release purpose was achieved whose sustained action was over 4months.（2）HPLC method is simple,precise and reliable,and is suitable for the determination of ivermectin in plasma.

关 键 词：伊维菌素缓释注射液 血药质量浓度 药代动力学 高效液相色谱法 

分 类 号：R944[医药卫生—药剂学]