Determination of tyrosine kinase inhibitor afatinib in rat plasma using LC-MS/MS and its application to in vivo pharmacokinetic studies of afatinib liposomes
| Autor: | Sha Liu, Meishan Han, Kaoxiang Sun, Xiucheng Yang, Xiaoyan Lu |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Male
Analyte Spectrometry Mass Electrospray Ionization Lung Neoplasms Afatinib Drug Compounding Clinical Biochemistry Pharmaceutical Science Antineoplastic Agents Chemical Fractionation 01 natural sciences Sensitivity and Specificity Analytical Chemistry Rats Sprague-Dawley Pharmacokinetics Drug Stability Tandem Mass Spectrometry Carcinoma Non-Small-Cell Lung Drug Discovery medicine Protein precipitation Animals Sample preparation Protein Kinase Inhibitors Spectroscopy Chromatography High Pressure Liquid Liposome Chromatography 010405 organic chemistry Chemistry 010401 analytical chemistry Selected reaction monitoring Reproducibility of Results 0104 chemical sciences Rats Injections Intravenous Liposomes Models Animal Afatinib Dimaleate medicine.drug Protein Binding |
| Zdroj: | Journal of pharmaceutical and biomedical analysis. 164 |
| ISSN: | 1873-264X |
| Popis: | A sensitive quantitative liquid chromatography-tandem mass spectrometry assay for afatinib in rat plasma was developed and validated using afatinib dimaleate as a standard. The analyte was determined to be ionized using the positive ion multiple reaction monitoring mode through electrospraying on an AB Sciex Triple Quad™ 4500 system. Protein precipitation was used for sample preparation, and an Agilent Eclipse XDB-CN column (100 × 2.1 mm, 3.5 μm) was applied for chromatographic separation. The mobile phase was water and methanol (15:85, v/v) containing 0.1% formic acid with a flow rate of 0.5 mL/min. The linear range was 0.5–200 ng/mL, with r2 = 0.9994 ± 0.0004 calculated from linear regression, with 1/x2 as the weighting factor for the calibration. The average recovery of the plasma samples was stable and reproducible. The analyte is sufficiently stable for handling and analysis. The pharmacokinetic study and comparison were performed by analyzing plasma concentrations in rats administered afatinib solution or prepared afatinib liposomes using the developed determination method. The Cmax of the afatinib liposomes was nearly 400-fold higher than that of the afatinib solution. These results indicate that liposome-encapsulation protected afatinib from endogenous protein binding, thereby reducing the risk of idiosyncratic drug reactions by protein adducts. Thus, Afatinib liposomes seem to be a promising strategy for the treatment of non-small cell lung cancer. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect