EDDP METABOLITE AS BIOMARKER FOR MONITORING OF
METHADONE SUBSTITUTION TREATMENT
DANIELA BACONI1, GABRIELA POPESCU1, ANNE-MARIE CIOBANU1*, MIRIANA STAN1, ANA MARIA VLĂSCEANU1, CRISTIAN BĂLĂLĂU2
1“Carol Davila” University of Medicine and Pharmacy, Faculty of Pharmacy, 6 Traian Vuia Street, Bucharest, Romania
2“Carol Davila” University of Medicine and Pharmacy, Faculty of Medicine, Sf. Pantelimon Emergency Hospital, 340 - 342
Pantelimon Avenue, Bucharest, Romania
*corresponding author: annemarieciobanu@yahoo.com
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Abstract:
Currently, the surveillance of methadone substitution treatment is considered an ongoing challenge, given the need for the
individualization of therapy and for increasing its efficiency. At present, although 2-ethyliden-1,5-dimethyl-3,3-
diphenylpyrrolidine (EDDP) is an inactive metabolite and consequently, it is assumed that the evaluation of its levels in
biological samples has no utility, there are discussions on the need for such determinations; thus, quantifying the urinary
EDDP metabolite levels could be useful to eliminate the false positive results of screening tests and to detect the possible
manipulation of urine samples by the patients. This study aimed to quantify methadone and its main metabolite EDDP, in the
patients’ urine, during methadone substitution treatment. The study group consisted of long-term heroin addicts, who were
under substitution therapy with methadone, with an average daily dose of about 72 mg. A liquid-liquid extraction procedure
(with hexane:isopropanol 97:3) of the urine samples and a GC-MS method for methadone and EDDP quantification were
applied. The results revealed a ratio between methadone and EDPP concentration supra unitary, showing a wide distribution
of both substances. This indicated a slow biotransformation of methadone (in poor metabolizer patients), suggesting a
possible liver pathology. Methadone concentrations were more variable than those of EDDP. No correlations between
methadone doses and methadone or EDDP urinary levels have been shown, but a statistically significant correlation between
methadone and its metabolite concentrations in urine has been depicted. These results indicate that EDDP can be used as a
biomarker for the monitoring of methadone substitution treatment, using the testing of urine sample in order to check for
compliance in patients stabilized with methadone.

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