Browsing School, Graduate by Author "Isenschmid, Daniel Stephan"
The role of ecgonine methyl ester in the interpretation of cocaine concentrations in postmortem blood.Isenschmid, Daniel Stephan; Caplan, Yale H. (1991)The metabolism and hydrolysis of cocaine (COC) was studied in vitro, in vivo and postmortem to determine if measuring concentrations of the COC metabolites, benzoyl-ecgonine (BE) and ecgonine methyl ester (EME) would facilitate the differential diagnosis of COC related Medical Examiner cases. In vitro, in unpreserved whole blood, COC hydrolyzed to EME. In blood preserved by a pseudocholinesterase inhibitor, a solution of acetylcholinesterase, and phosphate buffer controls, COC hydrolyzed to BE. COC incubated in a solution of pseudocholinesterase and carboxylesterase hydrolyzed to EME. The rate of hydrolysis of COC increased as the pH and temperature of the specimen increased. COC was stable in blood adjusted to pH 5 and preserved with sodium fluoride or organophosphates for at least 150 days at 4C or lower. An in vivo study in human subjects given intravenous and/or smoked COC confirmed that BE is the principal metabolite of COC in blood. All COC was accounted for by BE. EME, when present, did not exceed 5% of the BE concentration.;EME arises in postmortem blood mainly as a result of non-metabolic hydrolysis of COC. Thus, in unpreserved blood specimens, the EME concentration can be added to the COC concentration to estimate the blood COC concentration prior to in vitro hydrolysis, while BE would be attributable to prior COC metabolism. Application of this theory to a study of Medical Examiner cases supported this conclusion. COC in blood was determined between 1 and 8 days following death and again 10 to 70 days after further storage (N = 10). The COC lost was accounted for by the EME formed. Good correlation (r = 0.9677) was observed when the blood COC concentrations in Medical Examiner cases were compared to blood COC concentrations predicted by the addition of blood COC and EME concentrations; hence, analysis for EME and estimation of perimortem COC concentrations can assist in defining deaths associated with COC use.