Nov 27 2015
By Lynda Williams, Senior medwireNews Reporter
Chinese scientists have developed a fast and sensitive method for the quantification of the tyrosine kinase inhibitor (TKI) bosutinib in rat blood samples.
“The method has been successfully applied to a pharmacokinetic study of bosutinib in rats for the first time, which provides the basis for the further development and application of bosutinib”, say Meng-tao Zhou and co-authors from First Affiliated Hospital of Wenzhou Medical University.
They explain that the ultra-performance liquid chromatography with tandem mass spectrometry (UPLC–MS/MS) technique was developed to replace the existing high performance-liquid chromatography quantitative test for bosutinib in human serum which required “elaborate sample preparation” and had “low sensitivity”.
As reported in the Journal of Chromatography B, the test achieved “excellent linearity” for bosutinib in rat plasma at concentrations of 0.1–500 ng/mL with a lower limit of quantification (LLOQ) of 0.1 ng/mL. Precision – defined as the percentage relative standard deviation – was 8.5% and the test was found to be 4.7% accurate, as expressed in the percentage relative error between the measured and nominal values.
The UPLC–MS/MS technique was also tested in a rat pharmacokinetic study where samples were collected between 0.25 hours and 48 hours after the administration of oral bosutinib 50 mg/kg.
Plasma concentration versus time curves were charted and bosutinib 50 mg/kg was calculated to have an average half-life of 5.13 hours. The maximum concentration was an average of 407.89 ng/mL after 1.80 hours.
Zhou et al therefore conclude: “A rapid, sensitive, and specified method was developed and validated for the quantification of bosutinib.
“The method showed excellent performance as follows: low LLOQ (0.1 ng/mL), [wide] range (0.1–500 ng/mL), short running time (3.5 min), and simple preparation process.”
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