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

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。

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

Objective To study the preparation process of Ivermectins(IVM ) Sustained‐release Injections ,to develop an HPLC meth‐od for the determination of ivermectin concentration in sheep plasma ,and to study its pharmacokinetics in sheep .Methods (1)Sus‐tained‐release Injections were prepared by using castor oil as the solvent .(2)The content of IVM in IVM Sustained‐release Injec‐tions was determined by HPLC‐UV .The plasma samples were extracted with ethyl acetate .The analysis involved a Zirchrom C18 column (250 mm × 4 .6 mm ,5 μm)and methanol‐water (92∶8) as mobile phase .The flow rate was 1 .0 mL · 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 .0 ng · mL -1 and 20 .0‐200 .0 ng · mL -1 with correlation coefficients of 0 .997 7 and 0 .999 3 ;the limit of detection was 1 .8 ng · mL -1 ;the mean re‐covery 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 10 mg · kg -1 in sheep ,the main pharmacokinetics parameters were estimated to be as follows :tmax =8 .0 d ,Cmax =82 .3 ng · mL -1 ,AUC= 3 642 ng · d · mL -1 ,MRT=45 .9 d .Conclusion (1)By using the more diffi‐cult absorb solvent ,castor oil ,a long‐term sustained release purpose was achieved whose sustained action was over 4 months .(2) HPLC method is simple ,precise and reliable ,and is suitable for the determination of ivermectin in plasma .