International Journal of Molecular Sciences (May 2024)

A Tissue Distribution Study of Propafenone in an Intentional Fatal Poisoning Case

  • Žofia Nižnanská,
  • Alexandra Hengerics Szabó,
  • Marián Masár,
  • Roman Szucs,
  • Ján Šikuta,
  • Ľuboš Nižnanský

DOI
https://doi.org/10.3390/ijms25105202
Journal volume & issue
Vol. 25, no. 10
p. 5202

Abstract

Read online

Propafenone (PPF) belongs to the class 1C antiarrhythmics and can cause electrocardiogram-associated adverse/toxic effects. Cases of PPF intoxication are rarely investigated. We developed a novel and selective GC-MS/MS method for the determination of PPF and its tissue distribution in an intentional fatal poisoning case, which is applicable to PPF quantification in the range of therapeutic to lethal concentrations in complex post-mortem samples. A simple and effective sample pretreatment was applied to all analyzed samples. PPF was determined without the need for dilution, even in highly complex samples containing a wide range of analyte concentrations. Quantification was performed using the standard addition method, developed and validated according to the ICH M10 guidelines. The obtained results indicated that the PPF concentration in the serum from blood taken while alive, before therapy, was the highest ever reported in the literature. Despite the intensive therapy after the patients’ admission, the PPF concentrations in the lungs, spleen, femoral blood and cardiac blood were fatal or abnormally high. On the other hand, the concentrations in the liver and skeletal muscle were lower or approximately the same as observed in cases with therapeutic doses. To the best of our knowledge, the distribution of PPF has not been investigated in fatal intoxication cases and can be helpful in clinical or forensic toxicology.

Keywords