Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry Method Development and Pharmacokinetics of PTH-IA in Mice

Authors

• D Owusu-Ansah
• A Henning
• V DeGiorgi

Abstract

PTH-IA (parathyroid hormone receptor-inverse agonist) is a drug candidate under investigation for the treatment of Jansen’s Metaphyseal Chondrodysplasia (JMC) which is a rare disease of abnormalities in bone development and mineral ion homeostasis. The objective of the present study was to develop a rapid, accurate, and selective ultra-performance liquid chromatography-tandem mass spectrometry (UPLC–MS/MS) method to quantify PTH-IA in plasma samples and to assess PTH-IA pharmacokinetic (PK) properties in mice.
The developed UPLC-MS/MS method was successfully applied in PK studies of PTH-IA in mice. Following a single SC administration of 1.52 mg/kg to male C57Bl6 mice, the mean maximum plasma concentration (Cmax) was 152 ng/mL at the first sample collection time of 0.083 h. The terminal half-life (t1/2) was 2.3 h. The corresponding AUC0-‚àû was 101 ng‚àôh/mL. Following a single IV administration of 1.44 mg/kg, the mean plasma clearance (CLp) was relatively low, in the range of 10 - 15 mL/min/kg. The volume of distribution at steady-state (Vdss) was in the range of 0.21 - 0.45 L/kg. Based on the dose normalized AUC0-‚àû values between the SC and the IV studies, the estimated SC bioavailability for PHT-IA was 4 - 6% in mice.
An accurate, selective, rapid, and robust UPLC-MS/MS method to quantify PTH-IA in mouse plasma was developed. This method was applied successfully to the mouse PK studies.

Scientific Focus Area: Molecular Pharmacology

This page was last updated on Monday, September 25, 2023