Ultra-sensitive bioanalysis of the therapeutic peptide exenatide for accurate pharmacokinetic analyses at effective plasma concentrations utilizing UPLC-MS/MS

• Verfasst von: Sauter, Max [VerfasserIn]
• Verfasst von: Uhl, Philipp [VerfasserIn]
• Verfasst von: Burhenne, Jürgen [VerfasserIn]
• Verfasst von: Haefeli, Walter E. [VerfasserIn]
• Titel: Ultra-sensitive bioanalysis of the therapeutic peptide exenatide for accurate pharmacokinetic analyses at effective plasma concentrations utilizing UPLC-MS/MS
• Verf.angabe: Max Sauter, Philipp Uhl, Jürgen Burhenne, Walter E. Haefeli
• E-Jahr: 2020
• Jahr: 22 February 2020
• Umfang: 7 S.
• Fussnoten: Gesehen am 28.07.2020
• Titel Quelle: Enthalten in: Journal of pharmaceutical analysis
• Ort Quelle: Xi'an : Univ., 1994
• Jahr Quelle: 2020
• Band/Heft Quelle: 10(2020), 3, Seite 233-239
• ISSN Quelle: 2214-0883
• DOI: doi:10.1016/j.jpha.2020.02.008
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Exenatide
• Sach-SW: Intravenous
• Sach-SW: Nasal
• Sach-SW: Pharmacokinetics
• Sach-SW: Tandem mass spectrometry
• Sach-SW: UPLC
• K10plus-PPN: 1725646021

Abstract

Exenatide is the first approved glucagon-like peptide 1 receptor agonist subcutaneously or intramuscularly injected for the treatment of type 2 diabetes mellitus. Typical therapeutic plasma concentrations are in the low pg/mL range, therefore requiring ultra-sensitive quantification. To enable the accurate evaluation of pharmacokinetic studies, we established a UPLC-MS/MS assay with a lower limit of quantification (LLOQ) of 5 pg/mL (1.2 pM) using 200 μL of plasma, validated according to FDA’s and EMA’s pertinent guidelines. Exenatide was isolated from plasma with solid phase extraction utilizing anion-exchange sorbent. Quantification was performed with positive electrospray ionization tandem mass spectrometry in the selected reaction monitoring mode. The calibrated concentration range of 5-10,000 pg/mL was linear showing correlation coefficients >0.99. Interday and intraday accuracy ranged from 97.5% to 105.4% with corresponding precision of <10.9%. Accuracy at the LLOQ ranged from 93.0% to 102.5% with corresponding precision of <15.9%. Because of the validity of a 10-fold dilution QC (accuracy 111.2%), the assay is suitable for exenatide quantification up to 100,000 pg/mL. The ultra-sensitive assay’s applicability was demonstrated by the quantification of exenatide plasma concentrations and pharmacokinetics after intravenous and nasal administration to beagle dogs.