Abstract
The distribution of the racemic and the enantiomeric content of (+/-)-metoprolol was compared after ingestion of a massive fatal overdose of the racemic drug. Postmortem concentrations of the racemate in different tissues were assayed by gas chromatography after derivatization with trifluoroacetic acid anhydride. The distribution of the R- and S-enantiomers of metoprolol was analyzed by reversed-phase high-performance liquid chromatography. Metoprolol was extracted from postmortem specimens and derivatized with the chiral reagent 2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosyl isothiocyanate. The concentrations of active S(-)-isomer in blood, liver, and stomach contents were 33 mg/L, 224 mg/kg, and 56 mg/61 g, respectively. The concentrations of inactive R(-)-enantiomer in blood, liver, and stomach contents were 33 mg/L, 222 mg/kg, and 55 mg/61 g, respectively. These results indicate that half the total postmortem tissue concentration of metoprolol is the R-enantiomer, which is devoid of any beta-blocker activity.
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