A simple UPLC-MS/MS assay with a core-shell column for the determination of exemestane in human plasma for clinical application.

Exemestane is one of the aromatase inhibitors and has been used to treat breast cancer by lowering estrogen levels. Accurate quantification of exemestane is important to set an optimal dose, and thus a simple assay for exemestane is developed by ultra-performance liquid chromatography with tandem mass spectrometer. Exemestane was extracted from human plasma samples (100 μL) by simple protein precipitation with acetonitrile/methanol (1/1, v/v). Interference peaks observed close to the elution of exemestane led us to use a core shell column for higher selectivity instead of totally porous columns. The extracts were chromatographed on CORTECS UPLC C18, under a gradient elution at a flow rate of 0.25 mL/min and detected in the selected reaction monitoring. Validation parameters were assessed in accordance with the bioanalytical guidelines using quality control samples. Exemestane in human plasma was quantifiable from 0.5 to 50 ng/mL with high extraction recovery and minimal matrix effects. Hemolyzed or hyperlipemic plasma did not impact the exemestane assay. Exemestane was stable in human plasma for 392 days at -15°C or below. The developed assay was robust and successfully applied to quantifying exemestane concentrations in human plasma to support a clinical trial.