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目的:建立家兔血浆尼达尼布检测的高效液相色谱方法,研究尼达尼布在家兔体内的药动学。方法:采用ZORBAX SB-C18色谱柱为分离柱,以乙腈-0.1%三氟乙酸-水(35∶20∶45)为流动相,流速为1.0 ml·min~(-1),检测波长为286 nm,柱温为35℃;以卡马西平为内标,血浆在碱性条件下经乙酸乙酯萃取后检测。雄性家兔6只,按20 mg·kg~(-1)的剂量耳缘静脉注射给予尼达尼布;分别在给药前和给药后不同时间点耳缘静脉采集血液,分离血浆待测。用DAS 3.0计算药动学参数。结果:尼达尼布浓度在0.05~10.00μg·ml~(-1)范围内线性关系良好(r=0.999 8);低中高三个浓度(0.10,2.50,7.50μg·ml~(-1))的日内精密度RSD分别为5.55%、4.53%和2.74%,日间精密度RSD分别为6.15%、5.45%和3.15%;相对回收率分别为(98.50±5.47)%、(100.25±4.54)%和(99.94±2.74)%。6只家兔血浆尼达尼布浓度经DAS 3.0计算,尼达尼布的主要药动学参数如下:C_(max)为(3.01±0.35)μg·ml~(-1),t_(1/2)为(4.38±1.53)h,AUC_(0-t)为(11.67±1.71)μg·h·ml~(-1)。结论:该方法简便、快速、准确,适用于家兔血浆尼达尼布浓度的测定及其药动学研究。尼达尼布在家兔体内呈一级动力学消除。
OBJECTIVE: To establish a HPLC method for the detection of plasma ninhydrin in rabbits to study the pharmacokinetics of ninadap in rabbits. Methods: The mobile phase was acetonitrile-0.1% trifluoroacetic acid-water (35:20:45) with the mobile phase of ZORBAX SB-C18 as the separation column at the flow rate of 1.0 ml · min -1. The detection wavelength was 286 nm and the column temperature was 35 ℃. Carbamazepine was used as the internal standard and the plasma was extracted with ethyl acetate under alkaline conditions. Six male rabbits were given intravenous injection of nadirib at the dose of 20 mg · kg -1. Blood was collected from the marginal ear vein before administration and at different time points after administration, . Pharmacokinetic parameters were calculated using DAS 3.0. Results: The concentrations of nadinib in the range of 0.05 ~ 10.00μg · ml ~ (-1) had a good linear relationship (r = 0.999 8). The three concentrations of low, middle and high concentrations (0.10,2.50,7.50μg · ml -1) ), The intra-day precision RSD was 5.55%, 4.53% and 2.74% respectively. The intra-day precision RSD was 6.15%, 5.45% and 3.15%, respectively. The relative recoveries were (98.50 ± 5.47)% and (100.25 ± 4.54) % And (99.94 ± 2.74)%. The plasma concentrations of nindenib in six rabbits were calculated by DAS 3.0. The main pharmacokinetic parameters of nisinib were as follows: C max 3.01 ± 0.35 μg · ml -1, t 1 / 2) was (4.38 ± 1.53) h, and the AUC_ (0-t) was (11.67 ± 1.71) μg · h · ml -1. Conclusion: This method is simple, rapid and accurate and is suitable for the determination of plasma concentration of nindenib in rabbits and its pharmacokinetics. Nedanjab was first-order kinetic elimination in rabbits.