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。
Objective：To develop an HPLC method for determination of P91024 in Beagle dog plasma and investigation 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 50 μL of 2 mol · L^- 1 sodium carbonate solution, mixed for about 1min, extracted the plasma with eyelohexane and evaporated the eyelohexane under nitrogen gas. Liquid chromatograph equipped with a 231 nm deteetor,a Shim -pack GVP -ODS（ 150 mm×4. 6 mm,5 μm） 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 calculated the key pharrnaeokinetics 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. Conclusion ：The method is proved to be convenient, sensitive and suitable for pharmaeokineties study of P91024 in Beagles.
出处
《药物分析杂志》
CAS
CSCD
北大核心
2007年第1期72-75,共4页
Chinese Journal of Pharmaceutical Analysis
