A New Validated HPLC-MS/MS Method for Quantification and Pharmacokinetic Evaluation of Dovitinib, a Multi-Kinase
Haitham AlRabiah1, Adnan A Kadi1, Haya I Aljohar1
1Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11459, Saudi Arabia.
Background:
Dovitinib (TKI 258) is a small-molecule multi-kinase inhibitor for the treatment of different types of cancer. There is currently no validated method for its quantitative determination; therefore, we aimed to develop a reliable method to assay dovitinib.
Method And Results:
An electrospray ionization tandem mass spectrometry (ESI-MS/MS) method was used to separate dovitinib using an analytical C18 column (50 × 2.1 mm, 1.8 μm) at 25°C. Bosutinib was used as the internal standard (IS). Dovitinib was extracted from mouse plasma using a precipitation procedure. The mobile phase consisted of 10 mM ammonium formate: acetonitrile (68:32, v/v, pH 4.3) run at a rate of 0.3 mL min-1. MS detection was performed in the positive ion mode. Multiple reaction monitoring transitions were 393→337 and 393→309 for dovitinib, and 530→141 and 530→113 for bosutinib. The investigated method was validated as a bio-analytical method based on FDA guidelines. The linearity of the developed method was over the range of 5-500 ng mL,-1 coefficient of determination (r2= 0.9998). The average intra-day recovery and relative standard deviation (RSD) of the quality control (QC) sample were 97.24% and 1.32%, whereas the overall inter-day accuracy and precision were 97.99% and 0.54%, respectively. Dovitinib was stable during sample storage and handling conditions. Furthermore, the dilution integrity of the method was demonstrated by good recovery (97-99%) and RSD values (0.5-0.7%).
Conclusion:
This method was selectively sensitive and exhibited no matrix effect, with an acceptable accuracy and precision according to the FDA guidelines. The developed method could be efficiently used for pharmacokinetic studies of dovitinib.
Insights
A new electrospray ionization tandem mass spectrometry (ESI-MS/MS) method accurately quantifies dovitinib (TKI 258) in mouse plasma. This validated bio-analytical method is suitable for pharmacokinetic studies of this multi-kinase inhibitor.
Area of Science:
- Analytical Chemistry
- Pharmacology
- Biochemistry
Background:
- Dovitinib (TKI 258) is a multi-kinase inhibitor used in cancer treatment.
- A validated quantitative method for dovitinib determination is currently lacking.
Purpose of the Study:
- To develop and validate a reliable bio-analytical method for the quantitative determination of dovitinib in mouse plasma.
Main Methods:
- Electrospray ionization tandem mass spectrometry (ESI-MS/MS) was employed.
- Dovitinib was extracted from mouse plasma via precipitation.
- An analytical C18 column was used with a mobile phase of ammonium formate and acetonitrile.
- Bosutinib served as the internal standard.
Main Results:
- The method demonstrated excellent linearity (r²=0.9998) over the range of 5-500 ng/mL.
- High accuracy and precision were achieved, with intra-day recovery of 97.24% and inter-day accuracy of 97.99%.
- Dovitinib stability was confirmed during sample storage and handling.
Conclusions:
- The developed ESI-MS/MS method is selective, sensitive, and accurate.
- The method shows no matrix effect and meets FDA validation guidelines.
- This assay is suitable for pharmacokinetic studies of dovitinib in preclinical research.
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