壬苯醇醚-9胶囊在比格犬体内的药代动力学研究

A Pharmacokinetic Study of a Nonoxynol-9 Capsule in Female Beagle Dogs

目的建立一种快速、专属的反相高效液相色谱法测定比格犬血浆中壬苯醇醚-9的浓度,研究壬苯醇醚-9在比格犬体内的药代动力学。方法 6只健康♀比格犬,体质量9.5～10.0 kg,单剂量(192 mg/只)口服给药壬苯醇醚-9自制胶囊,采用DiamonsilTM(钻石)ODS柱(200 mm×4.6 mm,5μm,ID),以甲醇-水(95∶5)作为流动相,流速:1.0 ml/min,聚乙二醇辛基苯基醚为定量内标物,荧光检测的激发波长:226 nm,发射波长:300 nm,柱温:30℃,测定壬苯醇醚-9经时血药浓度,计算药代动力学参数。结果壬苯醇醚-9在0.1～10.0μg/ml范围内线性关系良好,日内、日间精密度均小于10%,低、中、高(0.2、1.0、5.0μg/ml)3种浓度的方法回收率分别为(96.7±7.0)%、(103.4±6.8)%、(101.6±5.3)%。主要药代动力学参数为:t 1/2(11.81±2.94)h,t max(1.75±0.76)h,C max(8.58±1.11)μg/ml,AUC0-24(50.77±14.67)μg.h/ml,AUC0-∞(66.58±25.00)μg.h/ml,MRT(14.84±4.31)h。结论本法简便、灵敏度高、专属性好,可以满足壬苯醇醚-9在比格犬体内的药代动力学研究。

Objective To establish a reversed-phase high performance liquid chromatography method for the determination of the plasma concentration of nonoxynol-9 and for the pharmacokinetic study of nonoxynol-9 in healthy female dogs.Methods A single dose of nonoxynol-9 was given to 6 healthy female dogs.Their plasma was collected and the concentration of nonoxynol-9 was determined by reversed-phase high performance liquid chromatography method using DiamonsilTM（diamond） ODS column（200 mm×4.6 mm,5 μm,ID） and a mobile phase of methanol-water（95：5） at a flow rate of 1.0 ml/min.TritonX-100 was used as the internal standard.The excitation and emission wavelengths were 226 nm and 300 nm,respectively.The column temperature was 30℃.Results The calibration curve of nonoxynol-9 showed good linearity over the range of 0.1-10.0 μg/ml.The intra-and inter-day precision was below 10%.The recovery at three concentrations（0.2,1.0,5.0 μg/ml） was（96.7±7.0）%,（103.4±6.8）%,（101.6±5.3）%,respectively.The main pharmacokinetic parameters of nonoxynol-9 were as follows：t1/2（11.81±2.94） h,tmax（1.75± 0.76） h,Cmax（8.58±1.11） μg/ml,AUC0-24（50.77±14.67） μg · h/ml,AUC0-∞（66.58±25.00） μg · h/ml.Conclusion The established method is simple,sensitive and specific,and can be used for the determination of the plasma concentration nonoxynol-9 and for pharmacokinetic studies.