Direct quantification of intact FIM in monkey plasma using a selective chromatography-tandem mass spectrometry

Shiqi Dong1, Aijie Zhang1, Yuan Gu2

  • 1Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China.

Insights

A new, simpler LC-MS/MS method was developed to quantify the FIM protein in monkey plasma. This method enables direct measurement of the novel GLP-1 analog, aiding in its pharmacokinetic studies.

Area of Science:

  • Pharmacology
  • Analytical Chemistry
  • Biochemistry

Background:

  • FIM protein, a novel GLP-1 analog, shows potential in treating Alzheimer's disease.
  • Existing methods for quantifying FIM protein in biological samples are complex and time-consuming.

Purpose of the Study:

  • To develop a simpler and more efficient LC-MS/MS method for direct quantification of intact FIM protein in monkey plasma.
  • To establish a reliable method for pharmacokinetic studies of FIM protein.

Main Methods:

  • Development of a direct LC-MS/MS method for FIM protein quantification.
  • Utilized an InertSustain Bio C18 column with a specific mobile phase (acetonitrile/water with formic acid).
  • Validated the method for linearity, precision, and accuracy in monkey plasma.

Main Results:

  • Achieved good linearity in the concentration range of 5-500 ng/ml (r² > 0.99).
  • Demonstrated acceptable intra- and inter-day precision (RSD: 2.30-12.8% and 7.30-13.2%) and accuracy (RE: -12.7-6.55% and -10.1-0.892%).
  • Successfully applied the method to a pharmacokinetic study in monkeys.

Conclusions:

  • The developed LC-MS/MS method is simpler and more efficient for direct quantification of intact FIM protein.
  • This method is suitable for pharmacokinetic analysis of FIM protein in biological matrices like monkey plasma.