Quantification of aconitine in post‐mortem specimens by validated liquid chromatography‐tandem mass spectrometry method: Three case reports on fatal ‘monkshood’ poisoning

Abstract

The diester-diterpene alkaloid aconitine was quantified by liquid chromatography-tandem mass spectrometry in post-mortem specimens of three cases where suicidal ingestion of Aconitum napellus L. ('monkshood') was supposed. In an attempt at rationalization, sample preparation and chromatographic conditions of plasma/serum drug analysis routine were utilized. Linearity was established from 0.5 to 20 µg L⁻¹ using newborn calf serum (NCS) as a surrogate calibration matrix for all sample types and mesaconitine as an internal standard. Validation (selectivity, sensitivity, precision, accuracy, recovery of the extraction procedure, matrix effect, processed sample stability) confirmed the applicability of the analytical method to various post-mortem matrices. Internal standard selection was based on multi-matrix process efficiency data. In human post-mortem peripheral blood a lower limit of quantification of 0.51 µg L⁻¹ and a limit of detection of 0.13 µg L⁻¹ were accomplished (0.1 ml sample aliquots). Aconitine was degraded to a large extent in different sample types when being stored at +20 °C for 30 days, while at -20 °C and for some matrices also at +4 °C no appreciable degradation occurred. Aconitine concentrations in real samples were 10.3-17.9 µg L⁻¹ (peripheral blood, n = 3), 14.9-87.9 µg L⁻¹ (heart blood, n = 3), 317-481 µg L⁻¹ (urine, n = 2), 609-4040 µg L⁻¹ (stomach content, n = 3), 139-240 µg L⁻¹ (bile, n = 2), 8.4 µg L⁻¹ (vitreous humor, n = 1), 54.7 µg L⁻¹ (pericardial fluid, n = 1), 492 µg kg⁻¹ (liver, n = 1), 15.2-19.7 mg L⁻¹ (unknown liquids secured onsite, n = 3). Together with concomitant circumstances the analytical data provided compelling evidence for acute Aconitum poisoning as being the cause of death.

Plasma vs heart tissue concentration in humans – literature data analysis of drugs distribution

“…Aconitine causes cardiovascular toxicity by interaction with voltage-sensitive sodium channels. According to Bicker et al [16] the concentration of aconitine in a fatality related to Aconitum napellus ingestion was three times higher in pericardial fluid than in peripheral blood [16]. Two other alkaloids, i.e.…”

Acute myocardial necrosis caused by aconitine poisoning: A case report

“…Yeih et al [ 4 ] reported a case of aconitine-induced life-threatening ventricular tachyarrhythmia that was successfully restored to normal sinus rhythm with amiodarone. Moritz et al [ 5 ] also described a case of acute arrhythmia caused by the ingestion of three homemade aconitine capsules, in which the half-life of aconitine in humans was calculated to be 3 h. Bicker et al [ 6 ] reported three cases of death resulting from aconitine poisoning and found that the aconitine concentration was significantly higher in heart blood than in peripheral blood.…”

A perfect refractory electrical storm by acute toxicity of accidental aconitine intake

“…The lethal dose for adults is about 5 mg, but a dose of 1 mg is often sufficient to cause severe cardiac rhythm disturbances and death. [6][7][8] Severe poisoning has been caused even by ingestion of 0.2 mg pure aconitine, or by decoctions with 6 g of Aconitum roots. 9 In 2 reported cases of voluntary intoxication and death, the autopsy revealed in both the same findings: blood congestion, hemorrhages in the lung tissue, lung edema and brain edema.…”