Distribution of metoprolol enantiomers in a fatal overdose.
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.
Mozayani
A
A
Medical Examiner's Office, Edmonton, AB, Canada.
Singer
P
P
Jones
G
G
D000293:Adolescent; D000319:Adrenergic beta-Antagonists / Q000009:adverse effects / Q000097:blood / Q000378:metabolism* / Q000493:pharmacokinetics; D002138:Calibration; D062787:Drug Overdose; D005260:Female; D005554:Forensic Medicine; D005753:Gastric Mucosa / Q000378:metabolism; D006207:Half-Life; D006801:Humans; D017879:Isothiocyanates / Q000737:chemistry; D008099:Liver / Q000378:metabolism; D008790:Metoprolol / Q000009:adverse effects / Q000032:analysis / Q000097:blood / Q000378:metabolism* / Q000493:pharmacokinetics; D012015:Reference Standards; D013237:Stereoisomerism; D014018:Tissue Distribution
D000319:Adrenergic beta-Antagonists; D017879:Isothiocyanates; C041943:2,3,4,6-tetra-O-acetylglucopyranosylisothiocyanate; D008790:Metoprolol