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

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

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.

Detaljer

Författare
  • Nico C van de Merbel
  • Peter Walland
  • Mikael Tiensuu
  • Carl Johan Sennbro
Enheter & grupper
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Miljömedicin och yrkesmedicin
Originalspråkengelska
Sidor (från-till)42-48
TidskriftJournal of Chromatography. B
Volym961
Utgåva nummerMay 14
StatusPublished - 2014
PublikationskategoriForskning
Peer review utfördJa