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

Our plain-English summary of HPLC-MS/MS method to measure trabectedin in tumors: preliminary PK study in a mesothelioma xenograft model, by L. Ceriani, M. Ferrari, M. Zangarini, et al (Bioanalysis, 2015).

The study

• Authors: L. Ceriani, M. Ferrari, M. Zangarini, S.A. Licandro, E. Bello, R. Frapolli, F. Falcetta, M. D'Incalci, R. Libener, F. Grosso, P. Aviles, M. Zucchetti
• Journal: Bioanalysis
• Published: 2015;7(15):1831-42
• Cited by: 6 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

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.

In plain English

This laboratory study developed and checked a method (HPLC-MS/MS) for measuring the anticancer drug trabectedin in tissue, then used it in mice carrying grafts of a human malignant pleural mesothelioma tumor called MPM-487. The study did not look at asbestos exposure. In the validation tests, the lowest amount the method could reliably measure in tumor was 0.60 ng/g. In tumor calibration samples tested over four days, the measured amounts averaged 96.1 to 102.1 percent of the amounts actually added. The mice received trabectedin intravenously at 0.10 mg/kg once a week for 4 weeks. After the last dose, samples were taken from three mice at each of five time points. The highest average level in plasma was 6.08 ng/ml. In tumor the highest level was 8.24 ng/g, reached at 4 hours, and 5.48 ng/g remained at 48 hours. Over the 48 hours after the last dose, drug exposure in tumor was 6.2 times that in plasma and 4.4 times that in liver. The authors concluded that trabectedin was preferentially distributed in the mesothelioma compared with plasma and normal tissue.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory method development and validation, with a preliminary drug-level (pharmacokinetic) experiment in mice
• Who was studied: Athymic female mice implanted under the skin with MPM-487 human malignant pleural mesothelioma tumor fragments from a biobank in Alessandria, Italy. For the drug-level study, three mice were sampled at each of five time points (1, 4, 8, 24 and 48 hours after the last dose).
• Exposure: Trabectedin (an anticancer drug) at 0.10 mg/kg intravenously once a week for 4 weeks. No asbestos exposure was studied.
• Main results:
  • In tumor, the lowest level the method could reliably measure was 0.60 ng/g.
  • In tumor calibration standards tested over four days, mean accuracy (measured as a percentage of the nominal concentration) ranged from 96.1 to 102.1 percent.
  • In tumor quality-control samples tested on different days, precision ranged from 6.0 to 8.2 percent and accuracy from 97.0 to 102.6 percent.
  • In mouse plasma, the mean peak trabectedin level was 6.08 ng/ml (7.98 nM).
  • In MPM-487 tumor, the peak level was 8.24 ng/g (10.82 nM), reached at 4 hours.
  • The tumor level was 5.48 ng/g (7.19 nM) at 48 hours.
  • Tumor drug exposure (AUC) over 0 to 48 hours after the fourth dose was 285.9 ng/g*h, which was 6.2 times the plasma AUC.
  • Over the same 0 to 48 hour window, the tumor-to-liver ratio of drug exposure (AUC) was 4.4.
• The authors' conclusion: The authors concluded that the method could measure trabectedin in tissues. They also concluded that trabectedin was preferentially distributed in mesothelioma compared with plasma and normal tissue.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Mesothelioma, Sarcoma, Ovarian Cancer.

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