Validated LC-MS/MS Method for Vibegron Quantification in Human Plasma via a Selective Fragment Ion (m/z 135.1):...

Area of Science:

• Analytical Chemistry
• Pharmacokinetics

Background:

• Vibegron is a therapeutic agent requiring precise quantification.
• Accurate measurement of vibegron in biological matrices is crucial for clinical studies.

Purpose of the Study:

• To develop and validate a sensitive and robust liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for quantifying vibegron in human plasma.

Main Methods:

• LC-MS/MS analysis using electrospray ionization in positive mode and multiple reaction monitoring (MRM).
• A stable isotope-labeled internal standard (vibegron ¹³C₅) was employed.
• Liquid-liquid extraction with ethyl acetate and addition of sodium fluoride for sample preparation.

Main Results:

• The method achieved excellent linearity (0.500-400.223 ng/mL), precision (0.58%-3.34%), and accuracy (98.26%-102.29%) using 100 μL of plasma.
• A novel MRM transition (m/z 445.5 → 135.1) was utilized for enhanced selectivity.
• The assay demonstrated consistent recovery (87.7%) and was fully compliant with ICH M10 guidelines.

Conclusions:

• The developed LC-MS/MS method is sensitive, robust, and suitable for quantifying vibegron in human plasma.
• This validated method can support future pharmacokinetic, bioavailability, and bioequivalence studies of vibegron.