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本研究建立并验证了一种简单、灵敏的液质联用方法用于测定裸鼠血浆中21-羟基地夫可特的浓度,并将此方法应用于药物动力学研究。选择倍他米松作为内标,血浆样品采用乙腈进行蛋白沉淀处理之后,用乙腈–4 mM甲酸铵溶液(用甲酸调节p H值至3.5,40:60,v/v)作为流动相,在C18反相色谱柱(50 mm×2 mm,5μm)中进行分离。质谱检测使用三重四级杆串联质谱,电喷雾正离子模式、质谱多反应监测技术对待测物21-羟基地夫可特和内标物倍他米松分别在质核比为400.2/124.0和393.3/147.0处进行检测。标准曲线的线性范围为0.5至400 ng/m L(r>0.99),日内日间的精密度为4.5%~10.1%,准确度为–1.7%~10.7%。运用该方法成功地进行了雌性Balb/c裸鼠口服单次给药4 mg/kg地夫可特的临床前药物动力学研究,采用一级吸收二室模型描述其药物动力学行为。
This study established and validated a simple and sensitive LC-MS method for the determination of 21-hydroxydefukotoc in plasma of nude mice and applied the method to pharmacokinetic study. Betamethasone was selected as the internal standard, and after the plasma samples were treated with acetonitrile for protein precipitation, acetonitrile-4 mM ammonium formate solution (pH value adjusted to formic acid to 3.5, 40:60, v / v) was used as the mobile phase, Reverse phase column (50 mm × 2 mm, 5 μm). Mass spectrometry detection using triple quadrupole tandem mass spectrometry, electrospray positive ion mode, mass spectrometry multiple reaction monitoring technology for the measured substance 21-hydroxy-fufukate and the internal standard betamethasone in the mass ratio of 400.2 / 124.0 and 393.3 / 147.0 Department for testing. The calibration curve has a linear range of 0.5 to 400 ng / mL (r> 0.99) with daily intra-day precision of 4.5% -10.1% and accuracy of -1.7% -10.7%. The preclinical pharmacokinetic study of a single oral administration of 4 mg / kg deflecte in female Balb / c nude mice was successfully performed using this method. The first-order absorption two-compartment model was used to describe the pharmacokinetics of deflazac.