盐酸吡格列酮滴眼剂在大鼠房水中最佳药物浓度测定  

Determination of best concentration of pioglitazone eye drops in rat aqueous humor

作　　者：桑璇[1] 陆晓和[2] 安美霞[1] 许汉春[1] 

机构地区：[1]南方医科大学第三附属医院眼科,广东省广州市510630 [2]南方医科大学珠江医院眼科,广东省广州市510280

出　　处：《眼科新进展》2013年第3期236-239,共4页Recent Advances in Ophthalmology

摘　　要：目的建立高效液相色谱法(high-performance liquid chromatographic,HPLC)测定眼局部使用盐酸吡格列酮(pioglita-zone,PIO)滴眼液后大鼠房水中PIO的浓度,探讨眼局部用药时PIO的角膜渗透性及有效性。方法将54只(108眼)SD大鼠随机分成5g·L(-1)、10g·L(-1)、20g·L(-1)PIO滴眼剂组,分别滴入滴眼剂各1滴,于给药后1h、2h、4h、6h、12h、24h共6个时间点抽取房水样品。采用Angilent Eclipse XDB-C18色谱柱为固定相,乙腈和磷酸盐缓冲液以体积比40:60(pH6.5)为流动相的HPLC检测不同时间点以上3种浓度PIO滴眼剂的房水中药物质量浓度。将质量浓度(C,mg·L(-1))对峰面积(AUC)作线性回归分析。结果利用HPLC检测PIO滴眼剂滴眼后大鼠房水中药物浓度的色谱图显示:PIO峰与流动相峰及房水峰能很好地分离,并无重合峰等干扰峰出现。给药后各个时间点的房水药物质量浓度之间差异有显著统计学意义(F=57.377,P=0.000),3种浓度滴眼剂在给药后4h房水中药物质量浓度均达到峰值;5g·L(-1)、10g·L(-1)、20g·L(-1)PIO滴眼剂组间大鼠眼房水中药物质量浓度比较,差异有显著统计学意义(F=68.477,P=0.000);从各个时间点看,三组间有显著性差异,且5g·L(-1)PIO组与10g·L(-1)、20g·L(-1)PIO组比较,差异有显著统计学意义(P<0.001)。10g·L(-1)PIO组与20g·L(-1)PIO组比较,除给药后1h时差异有显著性外,余时间点差异均无统计学意义(均为P>0.05)。结论 PIO滴眼剂眼局部使用具有良好的角膜渗透性,且要想达到一个安全有效的治疗目的,10g·L(-1)PIO滴眼剂为用药的最佳治疗浓度。Objective To develop a high-performance liquid chromatographic method for qualifying pioglitazone （PIO） in aqueous humor, and explore the permeabili- ty and effects of PIO eye drops for its clinical use in ophthalmology. Methods Fifty- four rats （108 eyes） was randomly assigned to three groups with 5 g · L-1 PIO,10 g · L- 1 PIO and 20 g · L - 1 PIO eye drops. Three concentration of PIO was topically adminis- trated on rat eyes, and the aqueous humor samples were taken at 1 hour, 2 hours, 4 hours,6 hours,12 hours and 24 hours after administration in each group. High-perform- ance liquid chromatography with Eclipse XDB-C18 colorimetric column as solid phase and acetonitrile： buffer phosphate （ pH 5.5 ; 40 ： 50, V/V） as mobile phase was used to determine the PIO concentration of aqueous humor at 1 hour,2 hours,4 hours,6 hours, 12 hours and 24 hours after administration. Linear regression analysis for mass concen- tration （ C, mg @ L- 1 ） and AUC was performed. Results The chromatograms of HPLC showed that the PIO peak could be separated from other materials, no interferential peak was seen. There was no statistical difference in PIO concentration in aqueous hu- mor among these six time points （F = 57. 377, P =0. 000 ）. After PIO eye drops was ad- ministrated four hours, the PIO concentration of aqueous humor was reach to peak val- ue. There was no statistical difference in PIO concentration in aqueous humor among 5 g · L-1 PIO group,10 g· L-1 PIO group,20 g · L-1PIO group（ F =68. 477 ,P =0.0000）. From each time points, the aqueous humor concentration of the 5 g ~ L- 1 PIO group de- creased significantly compared with 10 g · L-1 PIO group,20 g · L-1 PIO group（P 〈0. 001 ）. Except for 1 hour after administration,there was no statistical difference between 10 g · L-1 PIO group and 20 g · L- 1 PIO group among different time points （P 〉 0.05 ）. Conclusion PIO eye drops shows an acceptable permeation via the cornea. Moreover,in order to achieve a safe and effective treatmen

关 键 词：盐酸吡格列酮 高效液相色谱法 房水 

分 类 号：R977.15[医药卫生—药品]