2-Ethylidene-l,5-dimethyl-3,3-diphenylpyrrolidine

Fig. 1 Concentrations reported for opiods and cannabinoids in surface water of different European countries. MOR morphine Nor-MOR nor-morphine 6ACM 6-monoacetyl morphine HER heroin MET methadone EDDP 2-ethylidene-l,5-dimethyl-3,3 diphenylpyrrolidine THC A9-tetrahydro-cannabinol THC-COOH 11-nor 9-carboxy-THC N/A Values not availabe, not measured...

Racemic methadone (MET) is administered to heroin addicts as a substitution therapy. However, methadone enantiomers possess different pharmacological effects, and the drug has been demonstrated to be enantioselectively metabolized to its two major metabolites, 2-ethylidene-l,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) and 2-ethyl-5-methyl-3,3-diphenyl-l-pyrroline (EMDP). Stereoselective separation of MET, EDDP, and EMDP using an alpha-glycoprotein stationary phase and MS-MS detection was proposed by Kelly et al. [34]. Optimal separation conditions were 20 mM acetic acid isopropanol (93 7, pH 7.4), with a flow rate of 0.9mL/min. 

Gas Chromatography. System GA—methadone RI 2148, 2-ethylidene-l,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) RI 2030, 2-ethyl-5-methyl-3,3-diphenyl-l-pyrroline (EMDP) RI 1950 system GB—RI 2124 system GC—RI 2470 system GF— methadone RI 2370, EDDP RI 2280, EMDP RI 2190. 

High Pressure Liquid Chromatography. System HA—methadone k 2.2, 2-ethylidene-l,5-dimethyl-3,3-diphenylpyrrolidine k 2.8,... 

After consumption of methadone, 20-60% is eliminated within the first 24 h, as much as 30% via the gut. Up to 30% of the methadone present in the urine is unchanged. The extent of excretion in the unchanged form increases with the size of the dose and with decreasing pH of the urine. Approximately half of the amount eliminated via the kidneys is broken down to the desmethyl derivative, almost all of which reacts, undergoing ring closure, to form 2-ethylidene-l,5-dimethyl-3,3-diphenylpyrrolidine (EDDP). Another cyclic demethylation product, 2-ethyl-5-methyl-3,3-diphenyl-l-pyrrolidine (EMDP) accounts for 5-10% of the consumed dose. 

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