Aim: To develop a sensitive HPLC method for the quantitation of sunitinib (SU) and its active metabolite N-desethyl-sunitinib (SU12662) in human plasma. Materials & methods: The analytes were extracted from 500 μl of plasma using liquid-liquid extraction followed by protein precipitation. Chromatographic separation of two analytes and internal standard, vandetenib, was achieved on a hydrophilic interaction liquid chromatography analytical column using a gradient program. Calibration curves were linear over the range of 10-250 ng/ml for both SU and SU12662. The method was validated according to the US FDA guidelines for bioanalytical methods. Accuracy of the method at 10 ng/ml for SU and SU12662 was 8.7 and 6.7%, respectively, and precision was 10.18% and 17.3%, respectively. Conclusion: This method allows a specific, sensitive and reliable determination of SU and SU12662 in human plasma in a single analytical run which makes it useful for therapeutic drug monitoring.
Keywords: HILIC; HPLC; N-desethyl sunitinib; UV-detection; metabolite; method development; sunitinib; therapeutic drug monitoring; tyrosine kinase inhibitors; validation.