Determination and Pharmacokinetic Study of Afatinib in Rat Plasma by UPLC-MS/MS
10.3969/j.issn.1008-049X.2018.06.007
- VernacularTitle:UPLC-MS/MS法检测大鼠血浆中阿法替尼浓度及其药动学研究
- Author:
Chenchen TANG
1
;
Chuanxiang ZHANG
;
Jintao TAN
;
Danfeng MA
;
Shuanghu WANG
;
Yunfang ZHOU
Author Information
1. 湖南省儿童医院药剂科 长沙410007
- Keywords:
Afatinib;
Pharmacokinetics;
UPLC-MS/MS;
Rat
- From:
China Pharmacist
2018;21(6):977-981
- CountryChina
- Language:Chinese
-
Abstract:
Objective: To establish an accurate and selective UPLC-MS/MS) method for the determination of afatinib in rat plas-ma. Methods: Protein precipitating by acetonitrile was used to prepare the samples. A CORTECS BEH C18column ( 50 mm × 2. 1 mm, 1. 6 μm) was used to separate the analytes at 40℃. The mobile phase consisted of acetonitrile and water (0. 1% formic acid) with the flow rate of 0. 4 ml·min-1. The analytes were quantified by multiple reaction monitoring ( MRM) mode with positive electrospray ionization, while the target fragment ions were m/z 486. 19→112. 1 for afatinib and m/z 557. 3→112. 15 for neratinib (IS). Results: The calibration curve obtained good linearity for afatinib within the range of 1–200 ng·ml-1(r=0. 998 1), and the LLOQ in rat plasma was 1. 0 ng/ml. The intra-and inter-day precisions were both≤9. 51% . The recovery of afatinib from plasma was above 77. 1% . After intragastric administration and intravenous administration of afatinib in rats, the t1/2was 7. 19 h and 2. 69 h, Cmax was 97. 78 ng·ml-1and 123. 37 ng·ml-1,and AUC(0-∞)was 1 505. 4 ng·ml-1·h and 405. 55 ng·ml-1·h, respectively. Con-clusion: The validated method can be applied in the pharmacokinetic study of afatinib at the intragastric and intravenous dosage of 10 and 2 mg·kg-1, respectively.
