Dose-concentration relationships of methadone and EDDP in hair of patients on a methadone-maintenance program

After controlled oral administration of D,L-methadone solution (15-260 mg/day) in the context of a methadone-maintenance program, concentrations of methadone and 2-ethylidine-1,5-dimethyl-3,3-diphenyl-l-pyrrolidine (EDDP), in head hair were determined (N=41), using a fully automated headspace solid-phase microextraction procedure in combination with gas chromatography and mass spectrometry (HS-SPME/GC/MS).Methadone was present in all samples in concentrations ranging from 0.25 to 13.29 ng/mg (mean 2.69±0.45 ng/mg). EDDP was also present in every sample in concentrations ranging from 0.05 to 2.17 ng/mg (mean 0.43±0.08). The concentration ratio methadone/EDDP was 7.5±5.7 in the proximal segments, but decreased to 4.8±1.4 in the distal segments. A statistically significant correlation between the intake dose and the methadone and EDDP concentrations in the subjects' hair could be established only in the proximal segments (r=0.913 for methadone and r=0.901 for EDDP), but not in the distal segments. In all, 131 segments analyzed, the correlation coefficient was r=0.760 for methadone and r=0.738 for EDDP. In comparison to the dose-concentration relationship reported in the literature, we found a better correlation with higher correlation coefficients especially in the proximal segments.However, owing to a broad distribution in the correlation between dosage and concentration, the determination of methadone and EDDP in hair holds only limited information about prior methadone administration.