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

Laura Ceriani, Mariella Ferrari, Monique Zangarini, Simonetta Andrea Licandro, Ezia Bello, Roberta Frapolli, Francesca Falcetta, Maurizio D'Incalci, Roberta Libener, Federica Grosso, Pablo Aviles, Massimo Zucchetti

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)1831-1842
Number of pages12
JournalBioanalysis
Volume7
Issue number15
DOIs
Publication statusPublished - Aug 1 2015

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Medical Laboratory Technology
  • Analytical Chemistry

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