Pharmacokinetics of Lixisenatide, a GLP-1 Receptor Agonist, Determined by a Novel Liquid Chromatography–Tandem Mass Spectrometry Analysis in Rats

Because of its greater binding affinity and longer half-life than native glucagon-like peptide-1 (GLP-1), the GLP-1 receptor agonist lixisenatide is commonly used to treat type 2 diabetes mellitus. This study aimed establish a simple robust liquid chromatography–tandem mass spectrometry (LC–MS/MS) approach for in vivo pharmacokinetic investigation. Methanol-based protein precipitation with formic acid was exploited plasma sample extraction, using esomeprazole as internal standard. Gradient elution 0.1% distilled water acetonitrile utilized chromatographic separation. Mass monitor MRM transition at m/z 810.8 → 129.2 lixisenatide. In rat plasma, had lower limit quantification 10 ng/mL. The LC–MS/MS applied describe pharmacokinetics rats following intravenous subcutaneous dosing. average 0.37 ± 0.06 h after injection. estimated bioavailability 2.17%. analysis might be relevant future research create novel dosage formulations other agonists optimal therapeutic effectiveness.