Related Experiment Video
Updated: Dec 22, 2025
Author Spotlight: Discovering New Alkaloids in Plants with Advanced Mass Spectrometry Techniques
Published on: March 8, 2024
Analysis of TRPA1 antagonist, A-967079, in plasma using high-performance liquid chromatography tandem
Obed A Gyamfi1, Nesta Bortey-Sam1, Abigail B Donkor1
1Department of Chemistry and Biochemistry, South Dakota State University, Box 2202, Brookings, SD, 57007, USA.
Abstract:
The noxious effects from exposure to toxic inhalation hazards (TIHs, such as isocyanates, chlorine, etc.) are known to be triggered by the activation of transient receptor potential ankyrin 1 (TRPA1) ion channel. Antagonists of TRPA1 have shown near complete attenuation of the noxious effects from TIH exposure. One of the TRPA1 antagonists, (1E,3E)-1-(4-fluorophenyl)-2-methyl-1-pentene-3-one oxime (A-967079), has shown impressive efficacy, high selectivity, high potency, and oral bioavailability. Although a validated method to quantify A-967079 in biological matrices is vital for the further development of A-967079 as a therapeutic agent, no method for its analysis from any matrix is currently available. Hence, a rapid and simple HPLC-MS/MS method was developed and validated to quantify A-967079 in rabbit plasma. The method presented here features an excellent LOD of 25 nM and a wide linear range (0.05-200 μM), with good accuracy and precision (100 ± 10.5% and <14.2% relative standard deviation, respectively). The stability of A-967079 in plasma was excellent for most of the storage conditions evaluated. The method was successfully applied to determine A-967079 from treated animals and it may facilitate the development of this TRPA1 antagonist as a therapeutic agent against the noxious effects of TIH exposure.
Insights
A new HPLC-MS/MS method quantifies the TRPA1 antagonist A-967079 in rabbit plasma. This validated method is crucial for developing A-967079 as a therapeutic agent against toxic inhalation hazards.
Area of Science:
- Pharmacology
- Analytical Chemistry
- Toxicology
Background:
- Toxic inhalation hazards (TIHs) activate the TRPA1 ion channel, causing noxious effects.
- TRPA1 antagonists show promise in mitigating TIH-induced harm.
- A-967079 is a potent and selective TRPA1 antagonist with oral bioavailability.
Purpose of the Study:
- To develop and validate a quantitative analytical method for A-967079 in biological matrices.
- To establish a reliable method for quantifying A-967079 in rabbit plasma for further therapeutic development.
Main Methods:
- Development and validation of a rapid and simple High-Performance Liquid Chromatography-tandem Mass Spectrometry (HPLC-MS/MS) method.
- Quantification of A-967079 in rabbit plasma.
Main Results:
- The HPLC-MS/MS method demonstrated an excellent Limit of Detection (LOD) of 25 nM and a wide linear range (0.05-200 μM).
- The method achieved good accuracy (100 ± 10.5%) and precision (<14.2% relative standard deviation).
- A-967079 exhibited excellent stability in plasma under most tested storage conditions.
Conclusions:
- A validated HPLC-MS/MS method for quantifying A-967079 in rabbit plasma has been successfully established.
- This method's robustness and sensitivity facilitate the advancement of A-967079 as a therapeutic agent.
- The method's application in treated animals supports its utility in preclinical research for TIH exposure.
More Related Videos
10:38Simultaneous Quantification of Selected Kynurenines Analyzed by Liquid Chromatography-Mass Spectrometry in Medium Collected from Cancer Cell Cultures
Published on: May 9, 2020
11:44Cellular Membrane Affinity Chromatography Columns to Identify Specialized Plant Metabolites Interacting with Immobilized Tropomyosin Kinase Receptor B
Published on: January 19, 2022
