Abstract
A bioanalytical assay for quizartinib -a potent, and selective FLT3 tyrosine kinase inhibitor- in mouse plasma was developed and validated. Salting-out assisted liquid-liquid extraction (SALLE), using acetonitrile and magnesium sulfate, was selected as sample pretreatment with deuterated quizartinib as internal standard. Separation was performed with reversed-phase liquid chromatography followed by detection with positive electrospray-triple quadrupole mass spectrometry in the selected reaction monitoring mode. The assay was successfully validated for mouse plasma in a 2-2000ng/ml calibration range with r(2)=0.9958±0.0028 (n=7) for linear regression with the inverse square of the concentration as a weighting factor. The within-run precision (n=18), between-run precision and accuracy were 2.9-6.0%, 4.5-8.9% and 91.7-109.4% respectively. The drug was stable under all relevant conditions. Finally, the assay was successfully applied in a pharmacokinetic pilot study in plasma of FVB/NRj mice treated with quizartinb orally.
| Original language | English |
|---|---|
| Pages (from-to) | 300-305 |
| Number of pages | 6 |
| Journal | Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences |
| Volume | 1061-1062 |
| DOIs | |
| Publication status | Published - 1 Sept 2017 |
Keywords
- Animals
- Benzothiazoles
- Chromatography, Liquid
- Female
- Linear Models
- Mice
- Phenylurea Compounds
- Protein Kinase Inhibitors
- Reproducibility of Results
- Tandem Mass Spectrometry