1. HPLC-MS/MS method to measure trabectedin in tumors: Preliminary PK study in a mesothelioma xenograft model
- Author
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Roberta Libener, Francesca Falcetta, Laura Ceriani, Maurizio D'Incalci, Pablo M. Aviles, Federica Grosso, Monique Zangarini, Massimo Zucchetti, Roberta Frapolli, Mariella Ferrari, Simonetta Andrea Licandro, Ezia Bello, Ceriani, L, Ferrari, M, Zangarini, M, Licandro, S, Bello, E, Frapolli, R, Falcetta, F, D'Incalci, M, Libener, R, Grosso, F, Aviles, P, and Zucchetti, M
- Subjects
Mesothelioma ,Spectrometry, Mass, Electrospray Ionization ,Clinical Biochemistry ,Analytical chemistry ,Mice, Nude ,Dioxoles ,Analytical Chemistry ,Mice ,Tandem Mass Spectrometry ,Tetrahydroisoquinolines ,medicine ,Distribution (pharmacology) ,Animals ,Humans ,Mouse tumor ,General Pharmacology, Toxicology and Pharmaceutics ,Antineoplastic Agents, Alkylating ,Animals, Antineoplastic Agents, Alkylating, Chromatography, High Pressure Liquid, Dioxoles, Female, Humans, Mesothelioma, Mice, Nude, Spectrometry, Mass, Electrospray Ionization, Tandem Mass Spectrometry, Tetrahydroisoquinolines, Trabectedin, Xenograft Model Antitumor Assays ,Trabectedin ,Chromatography, High Pressure Liquid ,Detection limit ,Chemistry ,Soft tissue sarcoma ,General Medicine ,medicine.disease ,Xenograft Model Antitumor Assays ,Medical Laboratory Technology ,Hplc ms ms ,Cancer research ,Female ,Ovarian cancer ,medicine.drug - 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.
- Published
- 2015