title: HPLC-MS/MS method to measure trabectedin in tumors: preliminary PK study in a mesothelioma xenograft model.
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.
  
  
  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.
  
  
  CONCLUSIONS
  The method was validated for measuring trabectedin in tissues. In a mesothelioma xenograft model, trabectedin distributed preferentially in tumor compared with liver.
authors: IRCCS- Istituto di Ricerche Farmacologiche Mario Negri, Oncology Department, Via La Masa 19, 20156 Milan, Italy.
authors: Laura
authors: L
authors: Ceriani
authors: IRCCS- Istituto di Ricerche Farmacologiche Mario Negri, Oncology Department, Via La Masa 19, 20156 Milan, Italy.
authors: Mariella
authors: M
authors: Ferrari
authors: IRCCS- Istituto di Ricerche Farmacologiche Mario Negri, Oncology Department, Via La Masa 19, 20156 Milan, Italy.
authors: Monique
authors: M
authors: Zangarini
authors: IRCCS- Istituto di Ricerche Farmacologiche Mario Negri, Oncology Department, Via La Masa 19, 20156 Milan, Italy.
authors: Simonetta Andrea
authors: SA
authors: Licandro
authors: IRCCS- Istituto di Ricerche Farmacologiche Mario Negri, Oncology Department, Via La Masa 19, 20156 Milan, Italy.
authors: Ezia
authors: E
authors: Bello
authors: IRCCS- Istituto di Ricerche Farmacologiche Mario Negri, Oncology Department, Via La Masa 19, 20156 Milan, Italy.
authors: Roberta
authors: R
authors: Frapolli
authors: IRCCS- Istituto di Ricerche Farmacologiche Mario Negri, Oncology Department, Via La Masa 19, 20156 Milan, Italy.
authors: Francesca
authors: F
authors: Falcetta
authors: IRCCS- Istituto di Ricerche Farmacologiche Mario Negri, Oncology Department, Via La Masa 19, 20156 Milan, Italy.
authors: Maurizio
authors: M
authors: D'Incalci
authors: Cytogenetic & Molecular Pathology Laboratory, SS Antonio e Biagio General Hospital, Alessandria, Italy.
authors: Roberta
authors: R
authors: Libener
authors: Oncology, SS Antonio e Biagio General Hospital, Alessandria, Italy.
authors: Federica
authors: F
authors: Grosso
authors: PharmaMar R&D, Madrid, Spain.
authors: Pablo
authors: P
authors: Aviles
authors: IRCCS- Istituto di Ricerche Farmacologiche Mario Negri, Oncology Department, Via La Masa 19, 20156 Milan, Italy.
authors: Massimo
authors: M
authors: Zucchetti
mesh_terms: D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000032:analysis / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004149:Dioxoles / Q000032:analysis / Q000378:metabolism*; D005260:Female; D006801:Humans; D008654:Mesothelioma / Q000188:drug therapy*; D051379:Mice; D008819:Mice, Nude; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D053719:Tandem Mass Spectrometry / Q000379:methods; D044005:Tetrahydroisoquinolines / Q000032:analysis / Q000378:metabolism*; D000077606:Trabectedin; D023041:Xenograft Model Antitumor Assays
chemical_list: D018906:Antineoplastic Agents, Alkylating; D004149:Dioxoles; D044005:Tetrahydroisoquinolines; D000077606:Trabectedin