Sensitive Detection of α-Conotoxin GI in Human Plasma Using a Solid-Phase Extraction Column and LC-MS/MS

Area of Science:

• Toxicology
• Analytical Chemistry
• Pharmacology

Background:

• α-conotoxin GI is a potent neurotoxin from *Conus geographus* venom.
• Lethal doses in humans are extremely low, necessitating accurate quantification.
• No established analytical methods exist for detecting α-conotoxin GI in biological samples.

Purpose of the Study:

• To develop and validate a sensitive method for quantifying α-conotoxin GI in human plasma.
• To establish a reliable tool for toxicological and clinical studies involving this venom peptide.

Main Methods:

• Solid-phase extraction (SPE) using a polystyrene-divinyl benzene copolymer column for sample cleanup.
• Liquid chromatography/electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) in multiple reaction monitoring (MRM) mode for detection.
• Method validation including linearity, recovery, precision, accuracy, and stability assessments.

Main Results:

• The method demonstrated high sensitivity with a lower limit of quantification (LLOQ) of 2 ng/mL.
• Excellent linearity (r > 0.996) was achieved over the range of 2.0 to 300.0 ng/mL.
• The method showed good precision (intra- and inter-batch < 8.61%) and accuracy, with stable results under various conditions.

Conclusions:

• A specific, sensitive, and reliable LC-ESI-MS/MS method was successfully developed for α-conotoxin GI quantification in human plasma.
• This validated method provides a crucial tool for future research and clinical monitoring of α-conotoxin GI exposure.