Rapid solid-phase extraction method to quantify [(11)C]-verapamil, and its [(11)C]-metabolites, in human and macaque...

Area of Science:

• Pharmacokinetics and Drug Metabolism
• Radiochemistry and Imaging
• Biomarker Quantification

Background:

• P-glycoprotein (P-gp) is a key efflux transporter impacting drug delivery to the brain and fetus.
• Positron emission tomography (PET) ligand [(11)C]-verapamil measures in vivo P-gp activity.
• Verapamil metabolism necessitates accurate quantification for interpreting P-gp activity.

Purpose of the Study:

• Develop a rapid solid-phase extraction (SPE) method.
• Separate and quantify [(11)C]-verapamil and its radiolabeled metabolites in plasma.
• Facilitate accurate P-gp activity assessment in PET studies.

Main Methods:

• High-performance liquid chromatography (HPLC) identified [(11)C]-D-617/717 as the major metabolite.
• Sequential and differential pH elution on C(8) SPE cartridges was employed.
• Recovery was validated using nonradioactive standards and HPLC analysis.

Main Results:

• SPE method achieved >85% recovery for verapamil and D-617/717.
• Significant plasma concentrations of D-617/717 and unknown polar metabolites were detected in humans and nonhuman primates.
• SPE and HPLC methods demonstrated comparable quantification accuracy.

Conclusions:

• The SPE method enables simultaneous processing of multiple samples in under 5 minutes.
• This rapid quantification is vital given the short half-life of Carbon-11.
• The method is a valuable tool for determining [(11)C]-verapamil and metabolite concentrations in plasma.