Enhanced chromatographic efficiency obtained with vacuum jacketed columns facilitates the rapid UHPLC/MS/MS-based analysis of fasiglifam in rat plasma

Abstract

The use of vacuum jacketed LC columns (VJC) to minimize on- and post-column band broadening to maximize chromatographic performance has been evaluated as a potential route to improved high throughput (HT) analysis. Here the use of the “VJC” approach has been applied to the HT bioanalysis of the antidiabetic GPR40 agonist drug fasiglifam in rat plasma samples obtained following a 5 mg/kg IV dose. The data obtained from a 1 minute VJC/MS-based analysis showed significant improvements compared to that from a conventional 2 minute UHPLC method for the drug. Notably, using VJC/MS with the rapid 1 min analysis provided a ca. 50% reduction in peak width coupled with a 2–5 fold higher peak response whilst doubling analytical throughput when compared to a conventional UHPLC/MS method. In addition, the increased resolution provided by the VJC system also improved the separation of fasiglifam from common matrix interferences such as co-extracted phospholipids thereby reducing the potential for matrix effects. The concatenation of these improvements suggests that the VJC approach may indeed provide a pathway to more sensitive, robust and high throughput drug bioanalysis, with particular advantages for drug discovery applications.