A separate assay of released and liposomal encapsulated eribulin in dog plasma by liquid chromatography with tandem mass spectrometry for its application to a pharmacokinetic study.

Abstract

Eribulin has been used as a drug for the treatment of metastatic breast cancer and liposomal formulation of eribulin is under development to achieve a wider therapeutic index. It is important to separately determine released and encapsulated drugs in systemic circulation for liposomal drugs. In this study, a separate assay method was developed for the determination of released and total (encapsulated + released) eribulin concentrations in dog plasma by liquid chromatography with tandem mass spectrometry. The released eribulin in dog plasma was separated by ultrafiltration of plasma samples. Obtained plasma ultrafiltrate and untreated plasma samples recognized as released and total eribulin, respectively, were subjected to protein precipitation for extraction of eribulin. Eribulin was quantifiable from 0.1ng/mL. Accuracy and precision of eribulin in both matrices were within±15 and 15%, respectively, indicating a robust assay. Released and total eribulin concentrations in plasma were determined after intravenous administration of the liposomal formulation of eribulin to dogs, resulting in minimal released eribulin in plasma. In conclusion, a robust method for released and total eribulin levels in dog plasma was developed and was successfully applied to a pharmacokinetic study in dogs to characterize the pharmacokinetic profiles.