Veratrum Alkaloid Determination in Four Cases of Veratrum Aqua Poisonings

Veratrum poisonings are described in the toxicology literature as multiple Veratrum species grow in different parts of the Northern Hemisphere and are occasionally ingested by mistake. Veratrum toxicity is attributed to the steroidal alkaloids contained in all parts of the plant. In Russia, Veratrum poisonings are more common since there is an over-the-counter Veratrum lobelianum–based tincture, Veratrum Aqua (VA), which is topically used for the treatment of lice infestation. Despite its toxicity, VA is misused in traditional medicine as a remedy for alcohol use disorder. We describe four cases of VA poisoning that occurred in Moscow, Russia. Three main V. lobelianum alkaloids (jervine, protoveratrine A (proA) and protoveratrine B) were determined in patient plasma and urine samples using liquid chromatography–tandem mass spectrometry (LC–MS/MS). Here, we describe a novel validated LC–MS/MS method for jervine and proA quantification. A simple and rapid liquid–liquid extraction with methyl tert-butyl ether was utilized for analyte extraction. Chromatographic separation was achieved using a Poroshell 120 EC-C18 column, and the total run time was 14 min. The lower limit of quantification was 0.1 ng/mL for jervine and proA in both plasma and urine. Biological samples were obtained upon hospital admission and during treatment, thus enabling to get a better understanding of the alkaloid elimination profile. Upon admission, plasma concentrations of jervine (concentration range: 0.10–5.01 ng/mL) prevailed over proA (concentration range: 0–0.67 ng/mL). At this time, proA already reached maximum concentrations in urine (concentration range: 0.15–37.70 ng/mL). Maximum concentrations of jervine in urine were observed 24 h after admission (concentration range: 0.10–9.55 ng/mL). In all cases, plasma concentrations of Veratrum alkaloids correlated with condition severity. Since none of the patients confirmed VA intake, instrumental analysis was the basis for the definitive diagnosis of VA poisoning.

The Correlation between Chemical Composition, as Determined by UPLC-TOF-MS, and Acute Toxicity ofVeratrum nigrumL. andRadix paeoniae alba

The eighteen incompatible medicaments is an important theory in traditional Chinese medicine. The theory suggests that drugs in the eighteen incompatible medicaments can be toxic when used together.Veratrum nigrumL. andRadix paeoniae albabelong to the eighteen incompatible medicaments and have been prohibited for thousands of years. This study offers preliminary insight into the mechanism and chemical constituents responsible for the incompatibility and toxicity of these two agents. Specifically, we performed toxicology studies to identify and quantify the constituent substances of the two agents. Experiments revealed that acute toxicity increases when the dose ofV. nigrumL. is higher than, or equal to, RPA. UPLC-TOF-MS analysis showed that, although the volumes ofV. nigrumL. were the same, the content of some veratrum alkaloids changed significantly and had a trend toward a highly positive correlationr≥0.8with toxicity. This suggests that the increased toxicity of theV. nigrumL. and RPA combination was due mainly to increased content of the special veratrum alkaloids. The cytotoxicity of veratridine in SH-SY5Y cells was decreased with increasing paeoniflorin concentrations. This study provides insight into the mechanism behind the incompatibility theory of TCM.