Determination of Ibrutinib in Rat's Plasma by HPLC and Study of Its Pharmacokinetics
- VernacularTitle:HPLC法检测大鼠血浆中依鲁替尼含量及其药动学研究
- Author:
Li ZHANG
1
;
Chunyang ZHU
;
Wanyi LIU
;
Xiangjun QIU
Author Information
1. 单县中心医院 山东单县274300
- Keywords:
Ibrutinib;
HPLC;
Plasma concentration;
Pharmacokinetics
- From:
China Pharmacist
2018;21(10):1776-1778
- CountryChina
- Language:Chinese
-
Abstract:
Objective: To develop an HPLC method for the determination of ibrutinib in rat's plasma, and study its pharmacoki-netics. Methods: The analytical column was packed with ZORBAX XDB-C18(150 mm×4. 6 mm,5 μm). A mixture of acetonitrile-wa-ter-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 wave-length was set at 258 nm. The column temperature was set at 30℃. Carbamazepine was used as the internal standard. Plasma was ex-tracted under alkaline condition and ibrutinib was detected. Nine SD rats were treated with single dose of ibrutinib 15 mg·kg-1by in-tragastric 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-1to 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:Cmaxwas(1 019.43 ±74.85)μg·L-1, Tmaxwas(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 t1/2was(8.57 ±1.47)h. Conclusion: The method is simple, rapid and accurate, and can be applied in the studies on the phar-macokinetics of ibrutinib.
