Determination of subnanogram concentrations of fentanyl in plasma by gas chromatography—mass spectrometry: Comparison with standard radioimmunoassay

Abstract

A method was devised to determine fentanyl plasma concentrations by GC—MS using selected-ion monitoring (SIM) with sufentanil as internal standard. This was compared with a commonly used commercial radioimmunoassay (RIA). Sample preparation for GC—MS involved basification of plasma then extraction using n-butyl chloride followed by concentration to dryness and reconstitution in toluene for chromatography. Using 1-ml plasma samples, the estimated limit of detection of fentanyl was 20 pg/ml. Blood samples for pharmacokinetic studies were split and assayed by GC—MS and RIA which had a limit of detection of 200 pg/ml. Pearson's r ( r=0.80, p<0.0001) indicated the methods were highly correlated at all plasma concentrations. Owing to the greater sensitivity of the method, GC—MS is recommended over RIA for subnanogram determination of fentanyl in plasma.