Analysis of GLP-1 receptor agonists (Semaglutide, Liraglutide etc.) from blood and dried blood spots by means of LC-MS

Code: 241A15MT

In 2024, the Glucagon-like-peptide-1 (GLP-1) analog Semaglutide has been included in the WADA monitoring program. While the underlying idea for the development of this peptide-based drug was the improved therapy of diabetes mellitus type II, the resulting anti-obesity properties cause an alarming run in the non-diabetic community (incl. athletes) for Semaglutide-containing drugs like Ozempic or Wegovy, presumably used for weight management purposes. The drug is administered once a week by subcutaneous injection of 0.25 to 2.5 mg and owns a half-life of approx. 8 days. In contrast to other peptide-based drugs, circulating time and levels are comparably high, thus, the analysis of blood and DBS samples by means of LC-MS appears sensible and advantageous. Due to the extensive metabolism and low renal clearance, neglectable levels of intact Semaglutide are excreted, and relatively non-characteristic metabolites appear in urine only.

Besides Semaglutide, also other GLP-1 receptor agonists are available (e.g. Liraglutide, Lixisenatid and Tirzepatide) as approved medications with comparable biological effects. Noteworthy, the most important analogs Semaglutide, Liraglutide and Tirzepatide share an incorporation of artificially modified lysine residues, which enables the aimed action profile after application. This modification facilitates the analysis by LC-MS considerably due to the explicitly unnatural property of these structures. In this study, it is planned to include several of these GLP-1 analogs into one testing procedure for blood and DBS samples. After successful development, also the analysis of post administration samples with paired blood/DBS and urine-samples from volunteers treated with different GLP-1 receptor agonists is planned in order to enable the comparison of plasma/whole blood and urine levels.