PharmChem Laboratories Inc (PCHM)

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Pharmchek - Netherlands Cancer Institute, Amsterdam

[PDF] Igitur - Universiteit Utrecht 2013

The research described in this thesis was performed at the Department of Pharmacy & Pharmacology of the Slotervaart Hospital / the Netherlands Cancer Institute, Amsterdam, The Netherlands and the Department of Medical Oncology of the Netherlands Cancer Institute, Amsterdam, The Netherlands.

Conclusion
We have developed and validated a sensitive and easy to perform HPLC-MS/MS method for analysis of sunitinib and N-desethyl sunitinib in human sweat samples. To our knowledge this is the first report of bio-analytical determination of sunitinib secretion in sweat of a patient. Human sweat samples are collected using PharmChekTM Drugs of Abuse Patches. The sweat patches with sunitinib and N-desethyl sunitinib are pre-treated by extraction with methanol and addition of internal standard sunitinib-2H10. A linear dynamic range from 1.0 to 200 ng/patch has been validated. Validation results show that the method is accurate and precise. From our patient samples we concluded that cumulative amounts of sunitinib and N-desethyl sunitinib could be easily detected in human sweat patches applied on the upper arm of a patient during seven consecutive days.

Abstract
Introduction. 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, determination of sunitinib and its active metabolite in sweat has not been reported yet.

Method.
A sensitive and accurate method for the determination of sunitinib and its active metabolite N-desethyl sunitinib 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 TM Drugs of Abuse patches to determine cumulative amounts of sunitinib and metabolite.

Results.
Validation of the LC-MS/MS method was performed over a range from 1.0-200 ng/patch with good intra- and interassay accuracies for sunitinib and N desethyl sunitinib. Ranges of 76- 119 and 7.9-10.5 ng/patch for cumulative secretion of sunitinib and metabolite, respectively, were found in patient samples. Conclusion. To our knowledge this is the first method for determination of cumulative secretion of sunitinib and N-desethyl sunitinib in human sweat samples. Sunitinib and its metabolite were easily detectable in sweat patches of a patient treated with sunitinib.


Bioanalysis and clinical pharmacology of tyrosine kinase inhibitors

Bioanalyse en klinische farmacologie van tyrosine kinase remmers
(met een samenvatting in het Nederlands)

Proefschrift
ter verkrijging van de graad van doctor aan de Universiteit Utrecht op gezag van de rector magnificus, prof.dr. G.J. van der Zwaan, ingevolge het besluit van het college voor promoties
in het openbaar te verdedigen op woensdag 13 februari 2013 des middags te 2.30 uur



http://igitur-archive.library.uu.nl/dissertations/2013-0121-200558/lankheet.pdf

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