Quantification of sunitinib and n-desethyl sunitinib in human edta plasma by liquid chromatography coupled with electrospray ionization tandem mass spectrometry: Validation and application in routine therapeutic drug monitoring

Nienke A.G. Lankheet, N. Steeghs, H. Rosing, J. H.M. Schellens, J. H. Beijnen, A. D.R. Huitema

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

26 Citaten (Scopus)

Samenvatting

BACKGROUND:: Given 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. METHODS:: For 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. RESULTS:: The 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. CONCLUSIONS:: This 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.

Originele taal-2Engels
Pagina's (van-tot)168-176
Aantal pagina's9
TijdschriftTherapeutic Drug Monitoring
Volume35
Nummer van het tijdschrift2
DOI's
StatusGepubliceerd - apr. 2013
Extern gepubliceerdJa

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