HPLC-MS/MS method to measure trabectedin in tumors: preliminary PK study in a mesothelioma xenograft model
Laura Ceriani1, Mariella Ferrari1, Monique Zangarini1
1IRCCS- Istituto di Ricerche Farmacologiche Mario Negri, Oncology Department, Via La Masa 19, 20156 Milan, Italy.
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.
Insights
A new method quantifies trabectedin (anticancer drug) in tissues. This anticancer agent distributes more in tumors than liver in preclinical models, aiding drug development.
Area of Science:
- Pharmacology
- Analytical Chemistry
- Oncology
Background:
- Trabectedin is an approved anticancer agent for soft tissue sarcoma and ovarian cancer.
- Preclinical data on trabectedin's tumor distribution are lacking.
- A method for quantifying trabectedin in neoplastic tissues is needed.
Purpose of the Study:
- To develop and validate a quantitative method for trabectedin in preclinical tumor tissues.
- To assess trabectedin's distribution in a mesothelioma xenograft model.
Main Methods:
- Validated an LC-MS/MS assay for trabectedin quantification.
- Determined assay parameters: recovery, sensitivity, linearity, precision, and accuracy.
- Applied the method to mouse tumor and liver samples from mesothelioma xenografts.
Main Results:
- The LC-MS/MS assay demonstrated high accuracy (96.1-102.1%) and precision (6.0-8.2%).
- The limit of quantification was 0.10 ng/ml.
- Trabectedin showed preferential distribution in tumor tissue compared to liver in xenografts.
Conclusions:
- A validated LC-MS/MS method is available for measuring trabectedin in tissues.
- Trabectedin preferentially distributes to tumors over liver in a preclinical mesothelioma model.
- This method supports further preclinical investigation of trabectedin's tumor distribution.
More Related Videos
08:57Sample Extraction and Simultaneous Chromatographic Quantitation of Doxorubicin and Mitomycin C Following Drug Combination Delivery in Nanoparticles to Tumor-bearing Mice
Published on: October 5, 2017
07:54Implantation and Monitoring by PET/CT of an Orthotopic Model of Human Pleural Mesothelioma in Athymic Mice
Published on: December 21, 2019