Methadone and EDDP in hair from human subjects following a maintenance program: results of a pilot study

Abstract

A specific method has been developed for the quantitative determination of methadone (MTD) and its major metabolite, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), in hair. An amount of 50 mg hair samples were incubated in 0.01 M HCl overnight at 60°C and deuterated internal standards of MTD and EDDP were added before extraction. Hydrolyzed solutions were extracted by automated solid-phase extraction procedure and analyzed on a gas chromatography (GC) coupled to a ion trap mass spectrometer (MS). Positive chemical ionization was used with acetonitrile as liquid reagent. The different validation parameters, linearity, repeatability, recovery and detection limits are presented. A relative standard deviation (R.S.D.) of 12 and 11% was obtained for the repeatability of MTD and EDDP, respectively. The limits of quantification (LOQ) was 0.05 ng/mg for MTD and 0.2 ng/mg for EDDP. A number of 26 hair samples from human subjects following a long-term MTD therapy were analyzed by this method. Blood samples of these subjects were analyzed with a routine method using a liquid–liquid extraction and GC/nitrogen phosphorus detector (NPD). MTD was quantified in blood and hair samples and EDDP found in 50% of the hair sample. A comparison was made between the concentrations found in blood or in hair and the dose administrated. This study could demonstrate that there is no relation between the administrated dose and MTD or EDDP concentrations in hair.