Pharmacokinetic Measurements of Exenatide in Rat Plasma by LC-MS/MS: A Case Study for the Application of Tandem Quadrupole Versus Quadrupole Time-of-Flight Methods

Purpose

Diabetes is a major global public health crisis with incidence rates tripling in the last twenty years alone. Treatment of these diseases is therefore a key area of focus for many drug developers and several therapeutics, such as the glucagon-like peptide 1 (GLP-1) agonist (GLP-1RA) semaglutide, have achieved recent clinical and commercial successes. Targeting GLP-1 signaling for therapeutic intervention of type 2 diabetes (T2D) is an established strategy with nine GLP-1RAs approved worldwide and many new GLP-1RAs in preclinical or clinical stages. In fact, exenatide was the first FDA approved GLP1RA in 2005 and this drug continues to be widely used for treatment of T2D today. Exenatide is a synthetic version of Exendin-4, a 39-amino-acid peptide (MW 4186.6 Da) found in the saliva of the Gila monster. Traditionally, exenatide pharmacokinetic (PK) measurements in plasma have been performed using immunoassay-based techniques (e.g., ELISA) but more recently, tandem quadrupole (QQQ) liquid chromatography (LC-MS/MS) techniques have been applied, expanding the available analytical toolbox for drug developers. Here, we present a comparison between QQQ and QToF methods for quantitating exenatide in rat plasma.