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A thorough LC-MS/MS strategy to quantify abaloparatide in rat plasma: method development, validation and application.

Ying Kong1, Xiangping Li1, Yan Li1

  • 1Yantai Key Laboratory of Nanomedicine & Advanced Preparations, Yantai Institute of Pharmaceutical Science, Shandong, 264000, China. qlyu@yimm.ac.cn.

Analytical Methods : Advancing Methods and Applications
|September 17, 2025
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Summary

A new liquid chromatography-tandem mass spectrometry method accurately quantifies abaloparatide in plasma. This sensitive technique supports abaloparatide development and peptide bioanalysis using LC-MS/MS.

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Area of Science:

  • Analytical Chemistry
  • Pharmacology
  • Biotechnology

Background:

  • Abaloparatide is a parathyroid hormone-related peptide analog for osteoporosis treatment in postmenopausal women.
  • High fracture risk necessitates effective osteoporosis management strategies.
  • Accurate quantification of abaloparatide in biological samples is crucial for its development and clinical application.

Purpose of the Study:

  • To develop a novel, rapid, sensitive, and robust liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for abaloparatide quantification in plasma.
  • To validate the developed LC-MS/MS method for accuracy, precision, and reliability.
  • To assess the stability of abaloparatide in plasma under various storage conditions.

Main Methods:

  • Plasma samples were prepared using protein precipitation.
  • Abaloparatide was separated using a positively charged surface hybrid column.
  • Quantification was performed using multiple-reaction mass spectrometry detection with selected ion transitions.
  • Method validation included accuracy, precision, recovery, matrix effect, and stability assessments.

Main Results:

  • The LC-MS/MS method demonstrated high sensitivity, quantifying abaloparatide in the range of 0.02 to 8 ng/mL.
  • The method exhibited excellent accuracy and precision, with acceptable recoveries for abaloparatide and the internal standard.
  • Abaloparatide stability was confirmed under various storage conditions, including 4°C, -80°C, and freeze-thaw cycles.
  • The method was successfully applied to a pharmacokinetic study in rats.

Conclusions:

  • This is the first mass spectrometry-based method for quantifying abaloparatide in plasma.
  • The developed LC-MS/MS method provides a reliable and sensitive tool for abaloparatide quantification.
  • This method may facilitate abaloparatide development and advance the application of LC-MS/MS in peptide bioanalysis.