Development and validation of a UPLC-HR-SIM method to quantify semaglutide for its pharmacokinetic study

Abstract

Aim: To develop a highly sensitive and interference-resistant ultra performance liquid chromatography (UPLC) coupled with high-resolution selected ion monitoring (HR-SIM) mass spectrometry method for the quantification of semaglutide in biological samples, and to apply it for pharmacokinetic analysis.

Method: The UPLC-HR-SIM method was utilized to quantify semaglutide in beagle plasma, requiring minimal sample pretreatment. The method demonstrated a lower limit of quantification (LLOQ) of 5.0 ng/mL for semaglutide in beagle plasma.

Results: Following intravenous (iv) administration at a dose of 0.030 mg/kg, the plasma concentration of semaglutide in beagles exhibited a multi-exponential decay pattern, with an average elimination half-life (t_1/2) of 44.90 ± 11.45 h.

Conclusions: The UPLC-HR-SIM method has proven to be a highly sensitive and robust approach for the quantification of peptide-based drugs. This method will enhance the understanding of the pharmacokinetics and pharmacodynamics of semaglutide and facilitate further research into the pharmacokinetics of other peptide therapeutics.

Keywords

Semaglutide / Quantification / LC-MS / HR-SIM / Pharmacokinetics

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