Dental Plaque Concentrations of Methadone, Morphine and Their Metabolites in Opioid Replacement Therapy and in Post-Mortem Cases.

Non-mineralized dental biofilm (plaque) has potential as novel alternative matrix in forensic toxicology to prove drug use. The incorporation of illicit and medicinal drugs in dental plaque could take place through direct contact after oral or nasal intake, which can lead to high drug levels in the oral cavity, or indirectly via the secretion of drug-containing saliva, e.g. after intravenous application. Therefore, plaque samples from patients in opioid replacement therapy (ORT) and post-mortem plaque samples were analyzed and the drug concentrations were compared. The study comprised 26 plaque samples from ORT patients with different daily doses which were analyzed for methadone, morphine and their respective metabolites. Plaque samples were taken directly before the oral administration of the regular daily dose. Seventeen post-mortem plaque samples were analyzed, either from cases of lethal drug intoxications or after pain therapy with morphine. Plaque analysis was performed using LC-MS/MS after liquid extraction with acetonitrile. Plaque concentrations in ORT for methadone and its metabolite EDDP ranged from 42 to approx. 49,000 pg/mg (median 1,300 pg/mg) and from below 10 to 610 pg/mg (median 31 pg/mg), respectively. Morphine plaque concentrations in ORT ranged from 120 to 480 pg/mg (median 400 pg/mg). In lethal intoxication cases plaque concentrations were generally at least one order of magnitude higher than in the study groups with therapeutic substance use. This data will help to interpret drug findings in plaque. Additionally, the EDDP/methadone concentration ratio in plaque was lower after oral intake with contamination of the oral cavity (e.g. syrup) compared to cases with suspected intravenous application of methadone and could therefore indicate the drug administration route.