论文部分内容阅读
目的建立用于检测更昔洛韦在家兔房水内药物浓度的HPLC法;并研究更昔洛韦滴眼液在家兔眼内的药动学行为。方法房水样品用20%(V/V)高氯酸沉淀蛋白后取上清液直接进样,HPLC法测定。色谱柱使用LiChrospher C18柱(150 mm×4.6 mm,5μm),流动相为乙腈-0.05 mol.L-1醋酸铵水溶液(0.4∶99.6,V/V)。流速为1.0 mL.min-1,柱温为30℃,检测波长为254 nm。结果房水样品中药物浓度为40.0~400.0μg.L-1时呈良好的线性关系,方程为ρ=0.009 5A-2.410 3,r=0.999 0,(n=6)。低、中、高3种浓度的方法学平均回收率为97.0%、98.7%和102.4%。低、中、高3种浓度的绝对回收率分别为95.0%、98.1%、99.4%。样品溶液在反复冻融条件下,含量基本保持不变,显示更昔洛韦在此条件下稳定性良好。日间和日内RSD均<5%。最低检测限(LOD)为20.0μg.L-1。家兔药动学研究表明,市售更昔洛韦滴眼液药-时曲线符合二室模型一级吸收。结论该方法具有专属性强、灵敏度高、重现性好,适合于更昔洛韦在家兔房水内的药物浓度测定及其在眼内的药动学研究。
Objective To establish a HPLC method for the determination of ganciclovir in rabbit aqueous humor and to study the pharmacokinetics of ganciclovir in rabbit eye. Methods Aqueous humor samples were precipitated with 20% (v / v) perchloric acid and supernatants were directly injected into the supernatant and determined by HPLC. The column was LiChrospher C18 (150 mm × 4.6 mm, 5 μm) and the mobile phase consisted of acetonitrile-0.05 mol·L-1 ammonium acetate aqueous solution (0.4:99.6, V / V). The flow rate was 1.0 mL.min-1, the column temperature was 30 ℃ and the detection wavelength was 254 nm. Results The aqueous solution showed a good linearity when the drug concentration was 40.0 ~ 400.0μg.L-1. The equation was ρ = 0.009 5A-2.410 3, r = 0.999 0, (n = 6). The methodological recoveries for low, medium and high concentrations were 97.0%, 98.7% and 102.4%, respectively. The absolute recoveries of low, medium and high concentrations were 95.0%, 98.1% and 99.4%, respectively. The sample solution under repeated freezing and thawing conditions, the content remained essentially unchanged, indicating that the stability of ganciclovir in this condition is good. Day and day RSD were <5%. The lowest limit of detection (LOD) was 20.0μg.L-1. Rabbit pharmacokinetic studies show that the sale of Ganciclovir eye drops - time curve in line with the two-compartment model of a absorption. Conclusion The method has the advantages of high specificity, high sensitivity and good reproducibility. It is suitable for the determination of ganciclovir in rabbit aqueous humor and its pharmacokinetics in the eye.