• Nienke A G Lankheet, N Steeghs, H Rosing, J H M Schellens, J H Beijnen, and A D R Huitema.
• Department of Pharmacy and Pharmacology, Slotervaart Hospital/The Netherlands Cancer Institute, Amsterdam, the Netherlands. n.lankheet@hotmail.com
• Ther Drug Monit. 2013 Apr 1;35(2):168-76.

BackgroundGiven the low therapeutic index, the large interindividual variability in systemic exposure and the positive exposure-efficacy relationship of sunitinib, there is a rationale for therapeutic drug monitoring (TDM) of sunitinib. To support TDM, a method for determination of sunitinib and its active metabolite (N-desethyl sunitinib) has been developed and validated.MethodsFor determination of sunitinib and N-desethyl sunitinib in human EDTA plasma samples, high-performance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS/MS) was used. Validation experiments according to Food and Drug Administration guidelines were performed. In addition, the results of 25 analytical runs with 58 patient samples using 8 calibrators and 3 levels of quality control (QC) samples per analysis were compared with the results of analyses using only 3 calibrators and 1 QC sample to accelerate sample turnaround time. The method comparison experiment was performed according to international guidelines.ResultsThe HPLC-MS/MS method was validated over a linear range from 2.5 to 500 ng/mL using 50 μL plasma volumes, with good intra- and interassay accuracy and precision. In addition, the mean of the absolute differences between the compared methods was only -0.66 ng/mL (mean of relative differences, -0.85%), which is not a clinically relevant difference.ConclusionsThis method has been applied successfully for routine TDM purposes for patients treated with sunitinib. Moreover, reliable results with a rapid turnaround time were obtained when performing a short analytical run containing only 3 calibrators and 1 QC sample.

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