title: 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 high-performance 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.
authors: Department of Pharmacy & Pharmacology, Slotervaart Hospital/The Netherlands Cancer Institute, Louwesweg 6, 1066 EC Amsterdam, The Netherlands. nienke.lankheet@slz.nl
authors: Nienke A G
authors: NA
authors: Lankheet
authors: Christian U
authors: CU
authors: Blank
authors: Henk
authors: H
authors: Mallo
authors: Sandra
authors: S
authors: Adriaansz
authors: Hilde
authors: H
authors: Rosing
authors: Jan H M
authors: JH
authors: Schellens
authors: Alwin D R
authors: AD
authors: Huitema
authors: Jos H
authors: JH
authors: Beijnen
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D001711:Biotransformation; D002138:Calibration; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000201:enzymology / Q000556:secondary; D002851:Chromatography, High Pressure Liquid / Q000592:standards; D003640:Dealkylation; D004334:Drug Administration Schedule; D005260:Female; D060831:Hand-Foot Syndrome / Q000209:etiology; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D057230:Limit of Detection; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D011758:Pyrroles / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D015203:Reproducibility of Results; D000077210:Sunitinib; D013542:Sweat / Q000378:metabolism*; D053719:Tandem Mass Spectrometry / Q000592:standards
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D047428:Protein Kinase Inhibitors; D011758:Pyrroles; D000077210:Sunitinib