Fatal poisoning with Taxus baccata: quantification of paclitaxel (taxol A), 10-deacetyltaxol, baccatin III, 10-deacetylbaccatin III, cephalomannine (taxol B), and 3,5-dimethoxyphenol in body fluids by liquid chromatography-tandem mass spectrometry.

T Grobosch, B Schwarze, D Stoecklein, T Binscheck

Berliner Betrieb für Zentrale Gesundheitliche Aufgaben (BBGes), Institute of Toxicology and Poison Information Centre Berlin, Berlin, Germany. grobosch@bbges.verwalt-berlin.de

Journal of analytical toxicology 2012 Jan-Feb

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This method development was to confirm the fatal ingestion of toxic yew plant material in postmortem samples (stomach content, urine, femoral blood, cardiac blood, bile, and brain tissue) collected from a 22-year-old man who committed suicide by ingesting yew leaves. The analytical method was based on a liquid-liquid extraction under alkaline conditions followed by LC-MS-MS analysis. Chromatographic separation was achieved by HPLC on a Kinetex C18 2.6u (100 × 3 mm) coupled to a QTRAP 5500 system. The method allows the simultaneous identification and quantification of the yew alkaloids taxoids paclitaxel (taxol A), 10-deacetyltaxol, baccatin III, 10-deacetylbaccatin III, cephalomannine (taxol B), and 3,5-dimethoxyphenol; the alkaloidal diterpenoids monoacetyltaxine, taxine B, monohydroxydiacetyltaxine, triacetyltaxine, and monohydroxytriacetyltaxine were also identified. The initial hypothesis of yew tree (Taxus baccata) poisoning was confirmed. The quantitative evaluation revealed taxoid concentrations ranging from 4.5 to 132 µg/L (stomach content), 1 to 200 µg/L (urine), <0.5 to 12 µg/L (cardiac blood), <0.5 to 7.3 µg/L (femoral blood), and 4.9 to 290 µg/L (bile). In brain tissue, none of these taxoids could be detected (<0.5 µg/L). In urine, after enzymatic hydrolysis, the concentration of 3,5-dimethoxyphenol (3,5-DMP) was 23,000 µg/L. The alkaloidal diterpenoids were found in all postmortem samples. The newly developed LC-MS-MS method enables the identification of alkaloidal and non-alkaloidal diterpenoids and 3,5-dimethoxyphenol in human body fluids and tissues for the confirmation of accidental or intentional poisonings with yew plant material.

Citation

T Grobosch, B Schwarze, D Stoecklein, T Binscheck. Fatal poisoning with Taxus baccata: quantification of paclitaxel (taxol A), 10-deacetyltaxol, baccatin III, 10-deacetylbaccatin III, cephalomannine (taxol B), and 3,5-dimethoxyphenol in body fluids by liquid chromatography-tandem mass spectrometry. Journal of analytical toxicology. 2012 Jan-Feb;36(1):36-43