Overcoming bioanalytical challenges in an Onglyza® intravenous [14C]microdose absolute bioavailability study with accelerator MS

Background: An absolute bioavailability study that utilized an intravenous [14C]microdose was conducted for saxagliptin (Onglyza®), a marketed drug product for the treatment of Type 2 diabetes mellitus. Concentrations of [14C]saxagliptin were determined by accelerator MS (AMS) after protein precipitation, chromatographic separation by UPLC and analyte fraction collection. A series of investigative experiments were conducted to maximize the release of the drug from high-affinity receptors and nonspecific adsorption, and to determine a suitable quantitation range. Results: A technique-appropriate validation demonstrated the accuracy, precision, specificity, stability and recovery of the AMS methodology across the concentration range of 0.025 to 15.0 dpm/ml (disintegration...