Development of an LC-MS/MS method for the quantification of sunitinib and its metabolites in human nail and skin.

Sunitinib is associated with a high incidence of hand-foot skin reaction (HFSR) that significantly affects the quality of life and treatment continuation of the patient. The relationships between the concentrations of sunitinib and its metabolites in tissues and the occurrence of HFSR are crucial to preventing it. Therefore, this study developed a quantitative method for measuring the concentrations of sunitinib and its metabolites in human nails and skin. In addition, we evaluated whether this method can be applied to measure these drug concentrations in clinical samples. Nails or skin were crushed, methanol was added, and the supernatant obtained by centrifugation was used for analysis. Sunitinib, its metabolites, and voriconazole (internal standard: IS) were analyzed using liquid chromatography/mass spectrometry with electrospray ionization in positive mode. All samples were processed in the dark, and the analysis time was 5 min/run. In nail samples, calibration curves were linear in the range of 40-2000 pg/mg for sunitinib and N-desethyl sunitinib and 4-200 pg/mg for sunitinib N-oxide. In skin samples, linearity was observed in the range of 400-6000 pg/mg for sunitinib and N-desethyl sunitinib and 8-120 pg/mg for sunitinib N-oxide. The intra- and inter-day precision and accuracy were within 15 %, with a lower limit of quantification of 20 %. Extraction recoveries were ≥ 80 %, and the coefficients of variation for the IS-normalized matrix coefficients were < 15 %. This method was successfully applied to quantify these compounds in the nails and skin of patients receiving sunitinib treatment.