Application and validation of a urinary methadone metabolite (EDDP) immunoassay to monitor methadone compliance.

A total of 1381 urine specimens were screened using a Microgenics CEDIA urinary primary methadone metabolite (2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine; EDDP) immunoassay (cut-off calibrator concentration of 100 microg/L) in combination with a Dade Behring EMIT urinary methadone immunoassay (cut-off calibrator concentration of 300 microg/L). Of these, 642 (46%) were found to be positive using the EDDP assay but only 541 (39%) were found to be positive by the methadone assay. Out of the 108 specimens which were EDDP-positive but negative by the methadone assay, 47 (7%) could not be confirmed as positive using the routine in-house method of gas chromatography incorporating nitrogen-specific detection. Of these 47 results, 38 were re-screened using a more sensitive gas chromatography-mass spectrometry (GC-MS) technique, which demonstrated the presence of EDDP in every case. There was insufficient specimen to analyse the remaining nine samples. There were seven specimens which gave negative results by the EDDP and GC-MS assays but which had methadone concentrations ranging from 4000 to 37,500 microg/L. These were therefore presumed to be 'spiked' with methadone, i.e. to have had methadone added to the specimen to yield positive screening results and simulate compliance. It is concluded that the Microgenics CEDIA EDDP assay is a sensitive and reliable technique to determine the compliance of subjects prescribed methadone for opiate detoxification and maintenance.