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目的建立快速、灵敏测定大鼠血浆中5-羟基-1,7-双苯-3-庚酮(DPHC,5-Hydroxy-1,7-diphenyl-3-heptanone)的LC-MS/MS方法,并应用于药动学研究。方法血浆样品经叔丁基甲醚萃取后进行分析,采用Kinetex XB-C_(18)色谱柱(2.10 mm×50mm,2.6μm),柱温40℃,以水(含0.01%甲酸)—甲醇(含0.01%甲酸)为流动相梯度洗脱,流速0.30 m L·min~(-1),ESI离子源,多反应离子监测(MRM),用于定量分析的离子对为m/z 283.3→265.1,内标化合物益智酮甲为313.1→137.0。结果 DPHC的线性范围为2.0~2 000.0 ng·mL~(-1)(r=0.995 7),最低定量限为2.0 ng·mL~(-1);提取回收率为75.62%~77.75%,基质效应为85.21%~90.24%;日内和日间精密度RSD均<15%。口服(po.)和静脉注射(iv.)DPHC主要药代动力学参数:C_(max)分别为(61.2±28.8),(246.7±6.7)ng·mL~(-1);t_(1/2)分别为(1.90±0.68),(0.34±0.20)h;AUC0-t分别为(100.4±33.8),(78.1±1.8)h·ng·mL~(-1)。结论本法经方法学验证,适用于大鼠血浆中DPHC浓度的测定,适合药动学研究。
Objective To establish a rapid and sensitive LC-MS / MS method for the determination of 5-hydroxy-1,7-diphenyl-3-heptanone in rat plasma, And applied to pharmacokinetic studies. Methods Plasma samples were extracted with tert-butyl methyl ether and analyzed by Kinetex XB-C 18 column (2.10 mm × 50 mm, 2.6 μm) at 40 ℃ with water (containing 0.01% formic acid) and methanol % Formic acid) was used as the mobile phase gradient elution at a flow rate of 0.30 m L · min -1. The ESI ion source and multiple reaction ion monitoring (MRM) were used. The ion pair used for quantitative analysis was m / z 283.3 → 265.1 The standard compound Puzzle ketone is 313.1 → 137.0. Results The linear range of DPHC was 2.0-2000.0 ng · mL -1 (r = 0.995 7) and the lowest limit of quantification was 2.0 ng · mL -1. The extraction recoveries ranged from 75.62% to 77.75% The effect was 85.21% -90.24%. The intra-day and inter-day RSD were <15%. The main pharmacokinetic parameters of DPHC were (61.2 ± 28.8) and (246.7 ± 6.7) ng · mL -1 for oral and intravenous (iv) 2) were (1.90 ± 0.68) and (0.34 ± 0.20) h, respectively; AUC0-t were (100.4 ± 33.8) and (78.1 ± 1.8) h · ng · mL -1, respectively. Conclusion This method is validated by methodology, suitable for the determination of DPHC concentration in rat plasma, suitable for pharmacokinetic studies.