HPLC-MS/MS method to measure trabectedin in tumors: preliminary PK study in a mesothelioma xenograft model

Bioanalysis. 2015;7(15):1831-42. doi: 10.4155/bio.15.117.

Abstract

Background: Trabectedin is an anticancer agent registered for the second-line treatment of soft tissue sarcoma and ovarian cancer. No preclinical data are available on its tumor distribution, so a method for quantification in neoplastic tissues is required.

Methods/results: We validated an LC-MS/MS assay determining the recovery, sensitivity, linearity, precision and accuracy in mouse tumor and liver samples. The limit of quantification was 0.10 ng/ml with a curve range of 0.10-3.00 ng/ml (accuracy 96.1-102.1%). Inter-day precision and accuracy of QCs were 6.0-8.2 and 97.0-102.6% respectively. The method was applied in mesothelioma xenografts treated with therapeutic doses.

Conclusion: The method was validated for measuring trabectedin in tissues. In a mesothelioma xenograft model, trabectedin distributed preferentially in tumor compared with liver.

MeSH terms

  • Animals
  • Antineoplastic Agents, Alkylating / analysis
  • Antineoplastic Agents, Alkylating / metabolism*
  • Chromatography, High Pressure Liquid / methods
  • Dioxoles / analysis
  • Dioxoles / metabolism*
  • Female
  • Humans
  • Mesothelioma / drug therapy*
  • Mice
  • Mice, Nude
  • Spectrometry, Mass, Electrospray Ionization / methods*
  • Tandem Mass Spectrometry / methods
  • Tetrahydroisoquinolines / analysis
  • Tetrahydroisoquinolines / metabolism*
  • Trabectedin
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents, Alkylating
  • Dioxoles
  • Tetrahydroisoquinolines
  • Trabectedin