摘要
目的:建立大鼠血浆依鲁替尼检测的高效液相色谱方法,用于药物动力学研究。方法:采用ZORBAX XDB-C_(18)色谱柱(150 mm×4. 6 mm,5μm),以乙腈-水-0. 1%三氟乙酸(42∶31∶27)为流动相,流速为1. 0 ml·min^(-1);检测波长258 nm,柱温为30℃。以卡马西平为内标,血浆在碱性条件下萃取后检测。9只SD大鼠单剂量灌胃给予依鲁替尼15 mg·kg^(-1),分别在给予依鲁替尼后不同时间点采血,用该方法检测血浆中依鲁替尼的浓度;用DAS程序计算药动学参数。结果:血浆依鲁替尼浓度在10～2 000μg·L^(-1)范围内线性关系良好(r=0. 999 7);低、中、高3个浓度(25,500,1 500μg·L^(-1))的日内精密度RSD分别为7. 11%,10. 41%,3. 19%,日间精密度RSD分别为2. 56%,1. 98%,3. 79%;回收率分别为(78. 91±2. 10)%,(86. 29±3. 97)%,(83. 61±2. 11)%。9只SD大鼠单剂量灌胃给予依鲁替尼15 mg·kg^(-1)后,主要药物动力学参数如下:C_(max)为(1 019. 43±74. 85)μg·L^(-1); T_(max)为(4. 78±1. 20) h; AUC_((0-36))为(10 417. 26±2 167. 51)μg·h·L^(-1); AUC_((0-inf))为(10 956. 72±2 491. 09)μg·h·L^(-1),t_(1/2)为(8. 57±1. 47) h。结论:该方法简便、快速、准确,适用于依鲁替尼的药物动力学研究。
Objective： To develop an HPLC method for the determination of ibrutinib in rat＇s plasma,and study its pharmacokinetics. Methods： The analytical column was packed with ZORBAX XDB-C_（18）（ 150 mm × 4. 6 mm,5 μm）. A mixture of acetonitrile-water-0. 1% trifluoroacetic acid（ 42 ∶ 31 ∶ 27） was used as the mobile phase with the flow rate at 1. 0 ml·min^-1. The detection wavelength was set at 258 nm. The column temperature was set at 30℃. Carbamazepine was used as the internal standard. Plasma was extracted under alkaline condition and ibrutinib was detected. Nine SD rats were treated with single dose of ibrutinib 15 mg·kg^-1 by intragastric administration. Blood samples were collected at different time points after ibrutinib administration. The plasma concentration of ibrutinib was detected,and the pharmacokinetic parameters were calculated by DAS software. Results： Excellent linear relationship was obtained within the range of 10 μg · L^-1 to 2 000 μg · L^-1（ r = 0. 999 7）. The intra-day RSDs were 7. 11%,10. 41% and 3. 19%,and the inter-day RSDs were 2. 56%,1. 98% and 3. 79% respectively for three concentrations（ 25,500 and 1 500 μg·L^-1）,the average recoveries were（ 78. 91 ± 2. 10） %,（ 86. 29 ± 3. 97） % and（ 83. 61 ± 2. 11） %,respectively. After intragastric administration of ibrutinib,the main pharmacokinetic parameters of ibrutinib were as follows： Cmax was（ 1 019. 43 ± 74. 85） μg·L^-1,Tmax was（ 4. 78 ± 1. 20） h,AUC（ 0-36）was（ 10 417. 26 ± 2 167. 51） μg·h·L^-1,AUC（ 0-inf）was（ 10 956. 72 ± 2491. 09） μg·h·L^-1,and t1/2 was（ 8. 57 ± 1. 47） h. Conclusion： The method is simple,rapid and accurate,and can be applied in the studies on the pharmacokinetics of ibrutinib.
作者
张立
朱春阳
刘婉仪
邱相君
Zhang Li;Zhu Chunyang;Liu Wanyi;Qiu Xiangjun(Central Hospital of Shanxian,Shandong Shanxian 274300,China;Medical College of Henan University of Science and Technology)
出处
《中国药师》
CAS
2018年第10期1776-1778,共3页
China Pharmacist
