Determination and Validation of a Solid-phase Extraction Gas Chromatography-mass Spectrometry for the Quantification of Methadone and Its Principal Metabolite in Human Plasma

This study aimed to develop a solid-phase extraction gas chromatography-selected ion monitoring-mass spectrometry method for the determination of methadone (MDN) and 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) in human plasma. The linear response was obtained over the concentration range from 10 to 2000 ng/mL for MDN and EDDP. The absolute recoveries of MDN and EDDP were 95.9%–98.9% and 94.8%–102.4%, with relative standard deviation (RSD) ranging from 1.8% to 2.7% and 1.8% to 3.9%, respectively. The intra- and interday precisions were found to be less than 5% for both analytes. The limits of detection of MDN and EDDP were 4 and 5 ng/mL, respectively. The presented method was convenient for therapeutic drug monitoring and pharmacokinetic studies in patients on heroin-assisted MDN therapy.