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Quantitative determination of the anti-tumor agent tasquinimod in human urine by liquid chromatography-tandem mass spectrometry.

van de Merbel, Nico C; Walland, Peter; Tiensuu, Mikael and Sennbro, Carl Johan LU (2014) In Journal of Chromatography. B 961(May 14). p.42-48
Abstract
Tasquinimod is an anti-tumor drug that is currently in clinical development for the treatment of solid cancers. After oral administration, tasquinimod and a number of its metabolites are excreted in the urine. The quantitative determination of tasquinimod in urine is challenging because of the required sensitivity (down to 0.1nM or 40pg/mL), the highly variable nature of this biological matrix and the presence of potentially unstable metabolites, which may convert back to the parent drug. In this article, an LC-MS/MS method is described for the determination of tasquinimod in human urine in the concentration range 0.1-200nM. Liquid-liquid extraction with n-chlorobutane was used to extract tasquinimod from 100μL human urine and to remove... (More)
Tasquinimod is an anti-tumor drug that is currently in clinical development for the treatment of solid cancers. After oral administration, tasquinimod and a number of its metabolites are excreted in the urine. The quantitative determination of tasquinimod in urine is challenging because of the required sensitivity (down to 0.1nM or 40pg/mL), the highly variable nature of this biological matrix and the presence of potentially unstable metabolites, which may convert back to the parent drug. In this article, an LC-MS/MS method is described for the determination of tasquinimod in human urine in the concentration range 0.1-200nM. Liquid-liquid extraction with n-chlorobutane was used to extract tasquinimod from 100μL human urine and to remove interfering endogenous urinary constituents. Reversed-phase liquid chromatography coupled to a triple quadrupole mass spectrometer equipped with an ESI source was used for quantification of tasquinimod in a 2.5-min run. A stable-isotope labeled internal standard was used for response normalization. The intra- and inter-day coefficients of variation (precision) as well as the bias (accuracy) of the method were below 7%. Although considerable conversion of conjugated tasquinimod metabolites back to parent drug was observed when incurred samples were stored at 37°C for a prolonged time, tasquinimod as well as its metabolites were sufficiently stable under all relevant sampling, storage and analysis conditions. The method was successfully applied to determine the urinary excretion of tasquinimod in healthy volunteers and patients with renal impairment after a 0.5-mg oral dose. (Less)
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organization
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type
Contribution to journal
publication status
published
subject
in
Journal of Chromatography. B
volume
961
issue
May 14
pages
42 - 48
publisher
Elsevier
external identifiers
  • pmid:24858264
  • wos:000337863300007
  • scopus:84901217775
ISSN
1873-376X
DOI
10.1016/j.jchromb.2014.05.007
language
English
LU publication?
yes
id
a145da37-81c1-4810-adc6-e29f0c80a825 (old id 4452621)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/24858264?dopt=Abstract
date added to LUP
2014-06-06 20:25:28
date last changed
2017-01-01 03:55:08
@article{a145da37-81c1-4810-adc6-e29f0c80a825,
  abstract     = {Tasquinimod is an anti-tumor drug that is currently in clinical development for the treatment of solid cancers. After oral administration, tasquinimod and a number of its metabolites are excreted in the urine. The quantitative determination of tasquinimod in urine is challenging because of the required sensitivity (down to 0.1nM or 40pg/mL), the highly variable nature of this biological matrix and the presence of potentially unstable metabolites, which may convert back to the parent drug. In this article, an LC-MS/MS method is described for the determination of tasquinimod in human urine in the concentration range 0.1-200nM. Liquid-liquid extraction with n-chlorobutane was used to extract tasquinimod from 100μL human urine and to remove interfering endogenous urinary constituents. Reversed-phase liquid chromatography coupled to a triple quadrupole mass spectrometer equipped with an ESI source was used for quantification of tasquinimod in a 2.5-min run. A stable-isotope labeled internal standard was used for response normalization. The intra- and inter-day coefficients of variation (precision) as well as the bias (accuracy) of the method were below 7%. Although considerable conversion of conjugated tasquinimod metabolites back to parent drug was observed when incurred samples were stored at 37°C for a prolonged time, tasquinimod as well as its metabolites were sufficiently stable under all relevant sampling, storage and analysis conditions. The method was successfully applied to determine the urinary excretion of tasquinimod in healthy volunteers and patients with renal impairment after a 0.5-mg oral dose.},
  author       = {van de Merbel, Nico C and Walland, Peter and Tiensuu, Mikael and Sennbro, Carl Johan},
  issn         = {1873-376X},
  language     = {eng},
  number       = {May 14},
  pages        = {42--48},
  publisher    = {Elsevier},
  series       = {Journal of Chromatography. B},
  title        = {Quantitative determination of the anti-tumor agent tasquinimod in human urine by liquid chromatography-tandem mass spectrometry.},
  url          = {http://dx.doi.org/10.1016/j.jchromb.2014.05.007},
  volume       = {961},
  year         = {2014},
}