Abstract— An enzyme radiochemical assay for p‐octopamine, m‐octopamine (norphenylephrine) and phenylethanolamine based on the N‐methylation of these amines by the enzyme phenylethanolamine N‐methyl transferase (S‐adenosyl‐l‐methionine: phenylethanolamine N‐methyl transferase (EC 2.1.1.28) has been developed. [3H]Methyl‐S‐adenosyl‐l‐methionine was used as methyl donor. The reaction products are converted to their dansyl derivatives and separated by TLC in three different solvent systems prior to liquid scintillation counting. The method exhibits a sensitivity of less than 10 pg for each amine and is suitable for the measurement of endogenous p‐octopamine levels in mammalian brain. The highest levels of p‐octopamine were found in the hypothalamus (3.4 ng/g) but despite the sensitivity of the assay, neither phenylethanolamine nor m‐octopamine could be detected. After MAO inhibition, however, both of these amines were found to be present. p‐Octopamine was increased substantially in all brain regions following the administration of an MAO inhibitor, whereas pretreatment with reserpine produced a significant decrease in the hypothalamus.
The objective of this research was to determine the concentrations and distribution of the atypical antipsychotic drug, quetiapine, in postmortem tissues from eight Medical Examiner cases. Quetiapine was isolated from liquid specimens and tissue homogenates by extraction at an alkaline pH into 1-chlorobutane. The 1-chlorobutane was decanted, and quetiapine, plus the internal standard (prochlorperazine), was back-extracted into 0.1N sulfuric acid. The acid layer was made basic, and quetiapine, plus the internal standard, was re-extracted into 1-chlorobutane. Quantitation was by gradient, high-pressure liquid chromatography on a C-8 ODS (2.1 x 150 mm, 5 mu) column with acetonitrile/0.1M ammonium hydroxide (pH 10) mobile phase and a photodiode array detector set at 258 nm. The apparent linear range of the assay was from 0.05 to 5.0 microg/mL. At known concentrations of 0.1 and 0.5, interday accuracy (n = 5) was 103.8 and 107.2%, respectively. Interday precision (% cv) at the same concentrations was 9.8 and 9.0, respectively. In the cases where quetiapine was not considered to have contributed to the death, the postmortem concentrations in blood, liver, and bile ranged between 0.15 and 2.7 mg/L (n = 6), 1.3 and 9.5 mg/kg (n = 8), and 10 and 46 mg/L (n = 5), respectively. In the one case involving a quetiapine overdose, concentrations in blood (19.8 mg/L), liver (12.6 mg/kg), and bile (161 mg/L) exceeded the ranges of concentrations determined in specimens from the quetiapine-unrelated deaths.
We have determined drug/metabolite concentrations and ratios of methadone (METH) to two of its metabolites (EDDP, 2-ethylidene-1, 5-dimethyl-3, 3-diphenylpyrrolidine; and EMDP, 2-ethyl-5-methyl-3,3-diphenylpyrroline) in postmortem peripheral blood and liver tissue by liquid chromatography/tandem mass spectrometry. The assays employed deuterated internal standards and multiple reaction monitoring (MRM) techniques. The assay linear range was 0.01-2.0 mg/l for each analyte. METH, EDDP, and EMDP were determined in liver and peripheral blood from 46 methadone-positive cases. METH and EDDP were detected in all specimens, whether blood or liver. EMDP was detected, only in liver, and only 17 cases, at concentrations much lower than those of EDDP. Concentrations of METH and EDDP in blood and liver from EMDP-positive cases were in ranges higher than, but overlapping with, concentrations in blood and liver from EMDP-negative cases. These data suggest that although METH is readily demethylated and cyclized to EDDP, in vivo, conversion to EMDP may be less efficient and its accumulation in postmortem tissues may be highly individual.
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