Retmana Irene A, Wang Jing, Schinkel Alfred H, Schellens Jan H M, Beijnen Jos H, Sparidans Rolf W
Utrecht University, Faculty of Science, Department of Pharmaceutical Sciences, Division of Pharmacoepidemiology & Clinical Pharmacology, Universiteitsweg 99, 3584 CG Utrecht, The Netherlands.
The Netherlands Cancer Institute, Department of Molecular Oncology, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
J Chromatogr B Analyt Technol Biomed Life Sci. 2017 Sep 1;1061-1062:300-305. doi: 10.1016/j.jchromb.2017.07.034. Epub 2017 Jul 23.
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=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.
