Profiling cholinesterase adduction: a high-throughput prioritization method for organophosphate exposure samples

Area of Science:

• Analytical Chemistry
• Biochemistry
• Toxicology

Background:

• Organophosphorus nerve agents pose significant public health risks.
• Accurate and rapid detection of exposure is critical for effective medical response.
• Existing methods may lack the throughput for mass exposure scenarios.

Purpose of the Study:

• To develop a high-throughput prioritization assay for detecting organophosphorus nerve agent exposure.
• To profile unadducted butyrylcholinesterase (BChE) and Ser-198 adducts in clinical samples.
• To enable rapid identification of samples requiring confirmatory analysis.

Main Methods:

• Development of a high-throughput prioritization method using immunomagnetic separation and HPLC-MS/MS.
• Incorporation of a ballistic gradient to profile unadducted BChE.
• Definition of 'hits' as samples with BChE Ser-198 adducts or no BChE present for confirmatory analysis.

Main Results:

• The assay achieved 96% accuracy in an initial blind screen, correctly identifying 67 of 70 samples.
• The method demonstrated no false-negatives.
• The assay was rated an 'excellent assay' for controls and a 'double assay' for clinical sample prioritization.

Conclusions:

• This is the first high-throughput assay for profiling Ser-198 BChE adduction in clinical samples.
• The method significantly enhances the ability to prioritize samples in mass exposure incidents.
• The assay facilitates efficient confirmatory analysis for organophosphorus nerve agent exposure.