aconitine and jesaconitine

Aconitum contains highly toxic alkaloids such as aconitine, hypaconitine, jesaconitine, and mesaconitine. Since Aconitum ingestion causes fatal intoxication, it is important to analyze aconitines and their metabolites in the blood. In forensic toxicology, postmortem drug redistribution is known as one factor that would hamper accurate evaluation of concentrations. Therefore, it is recommended to collect multiple blood samples from various sites and compare the results to avoid miss identification of causative compounds for intoxication. In this study, we evaluated aconitines and their metabolites in postmortem blood specimens from ten sites by QuEChERS extraction and liquid chromatography-tandem mass spectrometry (LC/MS/MS). The recovery rates and matrix effects of analytes were approximately 74-80% and 94-100%, respectively. The correlation coefficients were over 0.99. The validation studies revealed that accuracies and precisions were around 97-2% (intraday) and 100-4% (interday), respectively. Finally, the concentrations of aconitine and jesaconitine were from 2.72 to 7.20 ng/mL and from 14.9 to 26.3 ng/mL, respectively. The concentrations of mesaconitine were from 0.32 to 0.88 ng/mL in four samples and detected in two. The concentrations were highest in the right atrium and lowest in the femoral vein. Our results suggest that aconitine and jesaconitne are accumulated in right atrium blood after death, and that right atrium specimen is suitable for measuring aconitine compounds in fatal intoxication cases.

Topics: Aconitine; Aconitum; Chromatography, High Pressure Liquid; Chromatography, Liquid; Tandem Mass Spectrometry

Two people out of three who accidentally ate boiled aconite leaves died in 2012. This was a typical case of aconite poisoning in Japan: Aconite (Aconitum spp.) was mistakenly collected instead of Anemone flaccida, an edible wild plant. The leaves of these plants are quite similar to each other. Chemical analyses of the aconite plant left at the scene suggested intake of a fatal amount of aconitine alkaloids by each person. The collector, who died, had missed the botanical differences between the two plants, even though he owned a wild plant guidebook. A. flaccida should be collected with its flowers in order to aid positive indentification and avoid aconite poisoning.

Topics: Aconitine; Aconitum; Adult; Aged; Chromatography, High Pressure Liquid; Fatal Outcome; Female; Heart Arrest; Humans; Male; Middle Aged; Plant Leaves; Shock, Cardiogenic; Tachycardia, Ventricular; Tandem Mass Spectrometry

A simple method for the simultaneous determination of four aconitine analogues (AC; aconitine, HA; hypaconitine, MA; mesaconitine, JA; jesaconitine) in Aconitum plants (Aconitum subcuneatum NAKAI) and a food that caused food poisoning was developed, using liquid chromatography tandem mass spectrometry (LC/MS/MS). Aconitine analogues were extracted with 1 mmol/L HCl and then cleaned up with an Oasis HLB cartridge. The LC separation was performed with an octadecylated silica column (Develosil ODS-HG-5, 2.0 mm i.d. x 50 mm) at a flow rate of 0.2 mL/min, using A solution (5 mmol/L ammonium acetate dissolved in 0.1% acetic acid) and B solution (acetonitrile-THF=1 : 3), 90%A (0 min)-->60%A (15 min)-->const. (2 min). Mass spectral acquisition was performed in the positive mode and the analogues were targeted using multiple reaction monitoring (MRM) with electrospray ionization (ESI). The recoveries of aconitine analogues were 93-99% from Aconitum plants. The detection limits of AC, HA, MA and JA were 0.4, 0.4, 0.3 and 0.5 ng/g, respectively. The aconitine analogues, except JA, were detected in food that caused food poisoning at the level of 2.6-29.7 microg/g. These results indicate that the developed method is suitable for the determination of aconitine analogues in Aconitum plants and foods that cause food poisoning.

Topics: Aconitine; Aconitum; Chromatography, Liquid; Food Analysis; Foodborne Diseases; Tandem Mass Spectrometry

Aconite poisoning was examined in five patients (four males and one female) aged 49 to 78 years old. The electrocardiogram findings were as follows: ventricular tachycardia and ventricular fibrillation in case 1, premature ventricular contraction and accelerated idioventricular rhythm in case 2, AIVR in case 3, and nonsustained ventricular tachycardia in cases 4 and 5. The patient in case 1 was given percutaneous cardiopulmonary support because of unstable hemodynamics, whereas the other patients were treated with fluid replacement and antiarrhythmic agents. The main aconitine alkaloid in each patient had a half-life that ranged from 5.8 to 15.4 h over the five cases, and other detected alkaloids had half-lives similar to the half-life of the main alkaloid in each case. The half-life of the main alkaloid in case 1 was about twice as long as the half-lives in the other cases, and high values for the area under the blood concentration-time curve and the mean residence time were only observed in case 1. These results suggest that alkaloid toxicokinetics parameters may reflect the severity of toxic symptoms in aconite poisoning.

Topics: Accelerated Idioventricular Rhythm; Aconitine; Aconitum; Aged; Area Under Curve; Arrhythmias, Cardiac; Biotransformation; Chromatography, High Pressure Liquid; Drugs, Chinese Herbal; Electrocardiography; Female; Half-Life; Humans; Male; Middle Aged; Severity of Illness Index; Tachycardia, Ventricular; Tandem Mass Spectrometry; Toxicology; Ventricular Fibrillation; Ventricular Premature Complexes

The Aconitum species (Ranunculaceae) are widely distributed in northern Asia and North America. Their roots are popularly used in herbal medicines in China and Japan. Many cases of accidental, suicidal and homicidal intoxication with this plant have been reported; some of these were fatal because the toxicity of Aconitum is very high. It is thus important to detect and quantify Aconitum alkaloids in body fluids, with high sensitivity. We have developed a simple and sensitive method for measuring four kinds of Aconitum alkaloids (aconitine, hypaconitine, jesaconitine and mesaconitine) by LC/electrospray (ESI)-time-of-flight (TOF)-MS. For all of them, only molecular ions were observed at an orifice voltage of 75 V; at 135 V, base peaks corresponding to [M - 60 + H]+ ions were observed. These four compounds and methyllycaconitine (internal standard) in human plasma samples were purified by solid-phase extraction. The four extracted compounds were completely separated in mass chromatograms; the calibration curves showed good linearity in the range 10-300 ng/ml, and the detection limits were estimated to be 0.2-0.5 ng/ml. Using our method, we also determined the amounts of these compounds in tuber samples. The present method is applicable in clinical and forensic toxicology.

Topics: Aconitine; Aconitum; Blood Chemical Analysis; Chromatography, High Pressure Liquid; Humans; Plant Tubers; Sensitivity and Specificity; Spectrometry, Mass, Electrospray Ionization; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

Determination of four toxic Aconitum alkaloids, aconitine, mesaconitine, hypaconitine and jesaconitine, in blood and urine samples has been established using high-performance liquid chromatography (HPLC) combined with ultraviolet absorbance detection, solid-phase extraction and mass spectrometry (MS). These alkaloids were hydrolyzed rapidly in alkaline solution (half lives (t1/2)five months) and were unstable in solutions of methanol and ethanol (t1/2

Topics: Aconitine; Alkaloids; Chromatography, High Pressure Liquid; Drug Stability; Humans; Plants, Medicinal; Spectrometry, Mass, Fast Atom Bombardment; Spectrophotometry, Ultraviolet

Described here is a fatal case of accidental aconitine poisoning following the ingestion of aconite, Torikabuto, mistaken for an edible grass, Momijigasa. A 61-year-old man developed symptoms of nausea, diarrhea, and discomfort of the body about 2 h after the ingestion and was taken to an emergency room. Resuscitation and antiarrhythmic drugs were ineffective, and ventricular tachycardia and fibrillation developed and lasted for 6 h. He was transferred to a coronary care unit and complete sinus rhythm was obtained on an electrocardiogram 30 h after his admission. The patient fell into a coma and died of brain edema diagnosed by CT on the 6th day. Consent for autopsy was denied by the family but was given for gas chromatography/selected ion monitoring (GC/SIM) to analyze the toxicity of aconitine alkaloids in the blood and the urine. Only a faint amount of jesaconitine was detected, while aconitine, mesaconitine and hypaconitine were not detectable in the blood 24 h after ingestion. On the other hand, aconitine and its related alkaloids such as mesaconitine, jesaconitine, and hypaconitine were clearly detected in the urine.

Topics: Aconitine; Chromatography, Gas; Fatal Outcome; Forensic Medicine; Humans; Ion-Selective Electrodes; Male; Middle Aged; Plants, Edible; Poaceae; Poisoning

The role of the substituents at C3 and C8 of jesaconitine (1) on jesaconitine-induced analgesia and toxicity was examined. 3-O-Acetyljesaconitine (2), 3-O-anisoyljesaconitine (3), and 3-deoxyjesaconitine (6) showed dose-dependent analgesic action, and the potency of their compound-induced analgesia and toxicity was lower than those of 1. The most remarkable difference was found in the toxicity. The results indicate that the C3 hydroxy function of 1 participate in the induction of toxicity rather than of analgesia. 8-O-Linoleoyl-14-anisoylaconine (5), 8-O-methyl-14-anisoylaconine (7), 8-O-ethyl-14-anisoylaconine (8), 14-anisoylaconine (4) and 8-deoxy-14-anisoylaconine (9) showed lower activities than jesaconitine-induced analgesia and toxicity. The analgesic activity of 7 was almost the same as that of 8, but the toxicity of 7 was lower than that of 8. The analgesic activity of 9 was lower than that of 4, but the toxicities of both derivatives were not apparent. These facts indicate that the C8 function of 1 is important to the induction of analgesia and toxicity, and also that this function participates differently in the induction of the analgesia and toxicity. Subsequently, it was suggested that substituents at C3 and C8 of 1 played important roles of the induction of the analgesia and toxicity, and that the modes of this participation were not the same in analgesia and toxicity.

Topics: Aconitine; Analgesics; Animals; Mice; Mice, Inbred Strains; Plants, Medicinal