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Published:
Journal of Analytical Toxicology,
ISSN 0146-4760,
Volume 27, Number 1, January/February 2003,
pp. 47-52
CASE REPORT: Analysis of Flecainide and Two Metabolites
in Biological Specimens by HPLC: Application to a Fatal Intoxication
T. Benijts[1], D. Borrey[1], W.E. Lambert[1], E.A. De Letter[2],
M.H.A. Piette[2], C. Van Peteghem[1], and A.P. De Leenheer[1]
[1]Laboratorium voor Toxicologie, Universiteit Gent, Harelbekestraat 72, B-9000
Gent, Belgium and
[2]Vakgroep Gerechtelijke Geneeskunde, Universiteit Gent, Jozef Kluyskensstraat
29, B-9000 Gent, Belgium
A few days after her admittance to a hospital for a suicide attempt
with benzodiazepines, a 15-year-old girl was found dead in bed. At autopsy,
no specific anatomo-pathologic cause of death was identified. Systematic toxicological
analysis (HPLC–DAD, GC–NPD, and GC–MS) of postmortem blood
and urine revealed the presence of high concentrations of flecainide and its
two major metabolites. Flecainide is a class IC anti-arrhythmic drug causing
a decreased intracardiac conduction velocity in all parts of the heart. To identify
and quantitate flecainide together with its metabolites in blood, urine, and
other toxicologically relevant matrices, a new method was developed using high-performance
liquid chromatography with diode-array detection. All compounds were separated
on a Hypersil BDS phenyl column using water, methanol, and 1.5M ammonium acetate
in a gradient system. Chromatographic analysis was preceded by an optimized
solid-phase extraction procedure on RP-C18 extraction columns. The flecainide
concentrations in blood and urine were 18.73 and 28.3 mg/L, respectively, and
the metabolites were detected only in urine at the following concentrations:
9.4 mg/L for meta-O-dealkylated flecainide and 8.59 mg/L for meta-O-dealkylated
flecainide lactam. Based on these results, it was concluded that the suicide
was consistent with an overdose of this anti-arrhythmic drug.
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