title: 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.
authors.affiliation: FTC-Forensic-Toxicological Laboratory Ltd., Gaudenzdorfer Guertel 43-45, 1120, Vienna, Austria.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Bicker
authors.forename: Fabio
authors.initials: F
authors.lastname: Monticelli
authors.forename: Andreas
authors.initials: A
authors.lastname: Bauer
authors.forename: Gabriele
authors.initials: G
authors.lastname: Roider
authors.forename: Thomas
authors.initials: T
authors.lastname: Keller
mesh_terms: D000157:Aconitine / Q000032:analysis* / Q000097:blood / Q000506:poisoning* / Q000652:urine; D031841:Aconitum / Q000506:poisoning*; D000293:Adolescent; D000818:Animals; D001344:Autopsy; D002417:Cattle; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D005260:Female; D006801:Humans; D057230:Limit of Detection; D008297:Male; D008875:Middle Aged; D053719:Tandem Mass Spectrometry / Q000379:methods*; D061585:Voltage-Gated Sodium Channel Agonists / Q000032:analysis* / Q000097:blood / Q000506:poisoning* / Q000652:urine
chemical_list: D061585:Voltage-Gated Sodium Channel Agonists; D000157:Aconitine
keywords: Aconitum spp. poisoning; Internal standard; Liquid chromatography-tandem mass spectrometry; Post-mortem analysis; Validation