【摘要】 目的:建立测定 Beagle 犬血浆中 P91024浓度的 HPLC 法并进行 Beagle 犬体内的药物动力学研究。方法:取犬血浆0.5mL,加甲醇0.5 mL,涡旋1 min,加2 mol·L^-1碳酸钠溶液50 μL,涡旋1 min,加环己烷提取血浆样品,氮气流吹干后用甲醇溶解残渣,进行 HPLC 分析。色谱柱为 Shim-pack VP-ODS 分析柱（150 mm×4.6 mm,5μm）,Shim-pack GVP-ODS 预柱（10mm×4.6 mm）;流动相为甲醇-水（87∶13）;流速:1 mL·min^-1;柱温:30℃;测定波长:231 nm,外标法定量。6条 Beagle 犬灌胃给予 P91024,计算主要药动学参数。结果:在10.0～4000.0 ng·mL^-1范围内,P91024峰面积与浓度呈良好线性关系（r=0.9998）,最低定量浓度为10 ng·mL^-1,该法的提取回收率为90.4%～93.6%（n=5）,方法回收率为98.2%～104.2%（n=5）,日内精密度和日间精密度分别为4.0%～6.6%和6.1%～8.4%。Beagle 犬灌服 P91024 20 mg·mL^-1后,其主要药物动力学参数为 C_max=1493.5 ng·mL^-1,T_max=3.33 h,t_1/2β=11.68 h,MRT=8.58 h,AUC_0-∞=9305.1 ng·h·mL^-1。结论:本法灵敏、准确,适用于 P91024的血药浓度测定及药物动力学研究。更多还原

【Abstract】 Objective:To develop an HPLC method for determination of P91024 in Beagle dog plasma and investi- gation the in vivo pharmacokineties of P91024 in Beagle dog.Method:Transferred a portion of 0.5 mL Beagle dog plasma,added 0.5 mL methanol,and stirred for about 1 min,then added 50μL of 2 mol·L^-1 sodium carbonate so- lution,mixed for about 1 min,extracted the plasma with cyclohexane and evaporated the cyclohexane under nitrogen gas.Liquid chromatograph equipped with a 231 nm detector,a Shim-pack GVP-ODS（150 mm×4.6 mm,5μm） analytical column and a Shim-pack GVP-ODS（10 mm×4.6 mm） guard column.The flow rate was 1 mL·min^-1 with a mobile phase consisted of methanol-water（87:13）.Six Beagles were ig P91024 20 mg·mL^-1,then calcu- lated the key pharmacokinetics parameters.Results:The linear range of calibration curve was within drug plasma concentrations of 10.0-4000.0 ng·mL^-1 （r=0.9998）,the quantity limit concentration was 10.0 ng·mL^-1 （S/ N>10）,the extraction recoveries were 90.4%-93.6% （n=5）,the recoveries of methodology were 98.2%- 104.2% （n=5）,inter-day RSD and intra-day RSD were 4.0%-6.6% and 6.1%-8.4%,respectively.Conclu- sion:The method is proved to be convenient,sensitive and suitable for pharmacokinetics study of P91024 in Bea- gles.更多还原