Determination of sunitinib and its active metabolite N-desethylsunitinib in sweat of a patient

Abstract

Skin reactions are side effects of sunitinib therapy with an adverse impact on quality of life often necessitating dose reductions. For conventional antineoplastic agents, such as doxorubicin, previous studies have indicated a possible relationship between sweat excretion and the development of skin toxicity. However, the determination of sunitinib and its active metabolite in sweat has not yet been reported. A sensitive and accurate method for the determination of sunitinib and its active metabolite N-desethylsunitinib in human sweat was developed using highperformance liquid chromatography coupled to tandem mass spectrometry detection (LC-MS-MS). Sweat samples of a patient treated with sunitinib were collected using Pharmchek™Drugs of Abuse patches to determine cumulative amounts of sunitinib and metabolite. Validation of the LC-MS-MS method was performed over a range from 1.0 to 200 ng/patch with good intra- and interassay accuracies for sunitinib and N-desethylsunitinib. Ranges of 76-119 and 7.9-10.5 ng/patch for cumulative secretion of sunitinib and metabolite, respectively, were found in patient samples. To our knowledge, this is the first method for determination of cumulative secretion of sunitinib and N-desethylsunitinib in human sweat samples. Sunitinib and its metabolite were easily detectable in sweat patches of a patient treated with sunitinib.