Identification and Quantification of Thujone in a Case of Poisoning Due to Repeated Ingestion of an Infusion of Artemisia Vulgaris L.

Plants of the Artemisia genus are used worldwide as ingredients of botanical preparations. This paper describes the case of a 49-year-old man admitted to the emergency room at a Zurich hospital in a manic state after the ingestion of 1 L of an infusion of Artemisia vulgaris. Two monoterpenic ketones, α- and ß-thujone, are present in various concentrations in Artemisia spp., but adverse effects have previously been associated only with essential oil from Artemisia absinthium and attributed to the inhibition of gamma-aminobutyric acid receptors, with consequent excitation and convulsions. The aim of this work was to examine and quantify the possible presence of thujone in the patient's serum and urine. A High Performance Liquid Chromatography (HPLC) method with isocratic separation and fluorescence detection (FLD) was set up and validated. Serum thujone concentrations were found to be 27.7 ± 3.48 µg/mL at day 0 and 24.1 ± 0.15 µg/mL on day 1. Results were confirmed by a gas chromatography with flame ionization detection (FID). Poisoning due to thujone was thus confirmed, suggesting four possible scenarios: (1) an unusually high concentration of thujone in the A. vulgaris ingested; (2) chronic exposure as the cause of the poisoning; (3) low metabolic efficiency of the patient; (4) contamination or adulteration of the plant material with other Artemisia spp., for example, A. absinthium. PRACTICAL APPLICATION: These results could aid research in the field of adverse effects of botanicals, lead to better understanding and management of similar cases of poisoning, and promote more informed use of natural products.

Pharmacokinetics and disposition of monoterpene glycosides derived from Paeonia lactiflora roots (Chishao) after intravenous dosing of antiseptic XueBiJing injection in human subjects and rats.

AIM: Monoterpene glycosides derived from Paeonia lactiflora roots (Chishao) are believed to be pharmacologically important for the antiseptic herbal injection XueBiJing. This study was designed to characterize the pharmacokinetics and disposition of monoterpene glycosides. METHODS: Systemic exposure to Chishao monoterpene glycosides was assessed in human subjects receiving an intravenous infusion and multiple infusions of XueBiJing injection, followed by assessment of the pharmacokinetics of the major circulating compounds. Supportive rat studies were also performed. Membrane permeability and plasma-protein binding were assessed in vitro. RESULTS: A total of 18 monoterpene glycosides were detected in XueBiJing injection (content levels, 0.001-2.47 mmol/L), and paeoniflorin accounted for 85.5% of the total dose of monoterpene glycosides detected. In human subjects, unchanged paeoniflorin exhibited considerable levels of systemic exposure with elimination half-lives of 1.2-1.3 h; no significant metabolite was detected. Oxypaeoniflorin and albiflorin exhibited low exposure levels, and the remaining minor monoterpene glycosides were negligible or undetected. Glomerular-filtration-based renal excretion was the major elimination pathway of paeoniflorin, which was poorly bound to plasma protein. In rats, the systemic exposure level of paeoniflorin increased proportionally as the dose was increased. Rat lung, heart, and liver exposure levels of paeoniflorin were lower than the plasma level, with the exception of the kidney level, which was 4.3-fold greater than the plasma level; brain penetration was limited by the poor membrane permeability. CONCLUSION: Due to its significant systemic exposure and appropriate pharmacokinetic profile, as well as previously reported antiseptic properties, paeoniflorin is a promising XueBiJing constituent of therapeutic importance.

[An LC-MS/MS method for the simultaneous determination of amygdalin and paeoniflorin in human urine and application to urinary excretion study].

ABSTRACT: The study aims to develop an LC-MS/MS method for the simultaneous determination of amygdalin and paeoniflorin in urine samples, and to investigate their urinary excretion characteristics in healthy volunteers after intravenous infusion administration of Huoxue-Tongluo lyophilized powder for injection (HTLPI). The urine samples were extracted by methanol, and then separated on a Hedera ODS-2 column with a mobile phase of acetonitrile and 5 mmol · L(-1) ammonium acetate buffer solution containing 0.05% formic acid (20:80). Electrospray ionization source was applied and operated in the positive ion mode using MRM. The method exhibited good linearity over the concentration range of 0.03 -40 µg · mL(-1). The values on both the occasions (intra- and inter-day) were all within 15% at three concentration levels. No matrix effect and carry-over effect were observed. Amygdalin and paeoniflorin were stable in human urine under different storage conditions. Approximately 79.6% of the administered amount of amygdalin was excreted unchanged in urine within 24 h and which was 48.4% for paeoniflorin. The developed LC-MS/MS method can be applied to evaluate the urinary excretion of amygdalin and paeoniflorin.

Mechanisms for eliminating monoterpenes of sagebrush by specialist and generalist rabbits.

Pygmy rabbits (Brachylagus idahoensis) are one of only three vertebrates that subsist virtually exclusively on sagebrush (Artemisia spp.), which contains high levels of monoterpenes that can be toxic. We examined the mechanisms used by specialist pygmy rabbits to eliminate 1,8-cineole, a monoterpene of sagebrush, and compared them with those of cottontail rabbits (Sylvilagus nuttalli), a generalist herbivore. Rabbits were offered food pellets with increasing concentrations of cineole, and we measured voluntary intake and excretion of cineole metabolites in feces and urine. We expected pygmy rabbits to consume more, but excrete cineole more rapidly by using less-energetically expensive methods of detoxification than cottontails. Pygmy rabbits consumed 3-5 times more cineole than cottontails relative to their metabolic body mass, and excreted up to 2 times more cineole metabolites in their urine than did cottontails. Urinary metabolites excreted by pygmy rabbits were 20 % more highly-oxidized and 6 times less-conjugated than those of cottontails. Twenty percent of all cineole metabolites recovered from pygmy rabbits were in feces, whereas cottontails did not excrete fecal metabolites. When compared to other mammals that consume cineole, pygmy rabbits voluntarily consumed more, and excreted more cineole metabolites in feces, but they excreted less oxidized and more conjugated cineole metabolites in urine. Pygmy rabbits seem to have a greater capacity to minimize systemic exposure to cineole than do cottontails, and other cineole-consumers, by minimizing absorption and maximizing detoxification of ingested cineole. However, mechanisms that lower systemic exposure to cineole may come with a higher energetic cost in pygmy rabbits than in other mammalian herbivores.

[Identification of volatile components in rat urine after oral administration of "wu-hu-tang"].

OBJECTIVE: To identify the volatile components in rat urine after oral administration of "Wu-Hu-Tang" (WHT). METHOD: GC-MS technique was applied to analyzing urine samples. RESULT: Eighteen components were detected in the WHT-treated rat urine other than the corresponding control. Among them, 14 components were identified, and 7 were also found in the extract of WHT. CONCLUSION: The above detected components might be derived from WHT, and some of them are effective components of WHT.