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O34: Castor bean self-poisoning: Report of a case with blood and urine ricinine measurements
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Thursday 12 June 2014 / Toxicologie Analytique & Clinique (2014) 26, S15-S24
15% or accuracy outside of the 85-115% range in BM. Validation on the other matrices showed accuracy of 80-120% for all analytes, except for cyamemazine in kidney where accuracy was 135% at the high QC level. Precision was <15% for all parameters, except for 6-MAM and morphine in blood where it was slightly greater than 15% at high QC level (15.2% and 15.1%, respectively). The automated extraction protocol applied without modifications allows detection of the 12 further compounds at therapeutic concentrations in blood and in the alternative matrices. Conclusion. – An automated SPE protocol associated to GC-MS/MS analysis was developed for quantification of caffeine, cyamemazine, meprobamate, morphine and 6-MAM in 11 biological matrices. The performance of this assay allows application in forensic toxicology or pharmacokinetic studies. The extraction protocol can be used for targeted analysis of various basic drugs and, with optimization, for other drugs or screening procedures in complex matrices. It could thus be an interesting starting set for further development for laboratories seeking to optimize their activity and confronted to analysis of new compounds or new matrices.
FORENSIC TOXICOLOGY, WITH BLT SESSION 1 O34
Castor bean self-poisoning: Report of a case with blood and urine ricinine measurements G. Hoizey (1), A. Villa (2), M. Cheze (1), J. Langrand (2), S. Mohebbi (3), A. Muckensturm (1), G. Pepin (1), M. Deveaux (1), R. Garnier (2) (1) Laboratoire Toxlab, Paris, France ; (2) Centre antipoison de Paris, hôpital Fernand Widal, Paris, France ; (3) Service de réanimation médico-chirurgicale, hôpital privé d’Antony, Antony, France. Introduction. – Ricin is a highly toxic protein from the castor bean plant (Ricinus communis) and is among the deadliest natural poisons available. We report the case of a 23 year-old man who committed suicide through both oral and intravenous self-administration of a castor bean extract. Methods. – Since it has been shown that ricin determination in clinical or post-mortem samples was difficult in real cases, ricinine, another alkaloid present in small amount in the castor bean plant, was used as a surrogate biomarker of ricin intoxication. Ricinine determination was isolated from the samples by liquid-liquid extraction and quantitatively determined by a specific LC-MS/MS method dedicated to the screening of plant toxins. MRM transitions applied for ricinine MS/MS measurement were: m/z 165 > 138 (quantification ion), 165 > 93, 165 > 84 and 165 > 82. Case Report. – A 23 year-old man was referred to the emergency department three hours after a suicidal attempt with castor bean extract. He vainly tried an intravenous self-administration of a Ricinus communis seed decoction with trimipramine, then ate twenty seeds together with 1 200 mg trimipramine (Surmontil® 4%). On admission, he was conscious and fully orientated (GCS 15). Clinical examination only revealed tachycardia (128/min); EKG disclosed no conduction or repolarization abnormalities. Blood tests were unremarkable except for a mild hypokalemia (3.4 mmol/L). Febrile diarrhea occurred 35 hours after ingestion. Lymphangitis of the left arm was also observed and blood cultures revealed Gram + cocci, when urine culture was sterile. The clinical course was transitorily complicated by: hypoglycemia (2.91 mmol/L), hyponatremia (133 mmol/L), and hyperkalemia (5.4 mmol/L) which were symptomatically compensated. Hepatic enzymes and serum creatinine were always normal. Besides symptomatic support, the patient received antibiotics and his symptoms amended, when 25 hours after admission, he escaped, threw himself out of a window, and died.
Results. – Blood and urine samples had been taken 22 hours after castor bean seed self-administration and were submitted to the laboratory for analytical assessment. Blood and urine ricinine concentrations were respectively 46 and 720 ng/mL. Conclusion. – In this case, clinical signs and symptoms were consistent with a minor ricin poisoning. However, ricinine blood and urine concentrations were high, when compared with those measured in previous case reports. In our case, as in previous reports of castor bean poisoning, ricinine levels were poorly correlated with poisoning severity. As a matter of fact, the toxic effects of the plant are mainly due to ricin which is poorly absorbed in the digestive tract. Ricinine digestive absorption is much better, but its toxicity is much lower. As a consequence, high ricinine blood and urine levels can be observed after ingestion, together with mild systemic poisoning. On the contrary, a severe poisoning may result from parenteral administration of a small amount of the plant extract with associated low serum and urine levels of ricinine. O35
Fitness to drive and cannabis: Experimental and real-life case study validation of two blood THCCOOH thresholds to distinguish occasional users from heavy smokers C. Giroud (1), M. Fabritius (1, 2), M. Augsburger (1), H. Chtioui (3), B. Favrat (1) (1) Centre universitaire romand de médecine légale, Lausanne-Geneva; (2) Institut für rechtsmedizin, university of Bern; (3) Division of clinical pharmacology, centre hospitalier universitaire vaudois, Lausanne, Switzerland. Introduction. – THC-COOH has been proposed as a criterion to help to distinguish between occasional from regular cannabis users. However, to date this indicator has not been adequately assessed under experimental and real-life conditions. Methods. – We carried out a controlled administration study of smoked cannabis with a placebo. Twenty-three heavy smokers and 25 occasional smokers, between 18 and 30 years of age, participated in this study [Battistella G et al., PloS one. 2013;8(1):e52545]. We collected data from a second real case study performed with 146 traffic offenders’ cases in which the whole blood cannabinoid concentrations and the frequency of cannabis use were known. Cannabinoid levels were determined in whole blood using tandem mass spectrometry methods. Results. – Significantly high differences in THC-COOH concentrations were found between the two groups when measured during the screening visit, prior to the smoking session, and throughout the day of the experiment. Receiver operating characteristic (ROC) curves were determined and two threshold criteria were proposed in order to distinguish between these groups: a free THC-COOH concentration below 3 μg/L suggested an occasional consumption (≤ 1 joint/week) while a concentration higher than 40 μg/L corresponded to a heavy use (≥ 10 joints/month). These thresholds were successfully tested with the second real case study. The two thresholds were not challenged by the presence of ethanol (40% of cases) and of other therapeutic and illegal drugs (24%). These thresholds were also found to be consistent with previously published experimental data. Conclusion. – We propose the following procedure that can be very useful in the Swiss context but also in other countries with similar traffic policies: If the whole blood THC-COOH concentration is higher than 40 μg/L, traffic offenders must be directed first and foremost toward medical assessment of their fitness to drive. This evaluation is not recommended if the THC-COOH concentration is lower than 3 μg/L. A THC-COOH level between these two thresholds can’t be reliably interpreted. In such a case, further medical assessment and follow up of the fitness to drive are also suggested, but with lower priority.
Thursday 12 June 2014 / Toxicologie Analytique & Clinique (2014) 26, S15-S24
15% or accuracy outside of the 85-115% range in BM. Validation on the other matrices showed accuracy of 80-120% for all analytes, except for cyamemazine in kidney where accuracy was 135% at the high QC level. Precision was <15% for all parameters, except for 6-MAM and morphine in blood where it was slightly greater than 15% at high QC level (15.2% and 15.1%, respectively). The automated extraction protocol applied without modifications allows detection of the 12 further compounds at therapeutic concentrations in blood and in the alternative matrices. Conclusion. – An automated SPE protocol associated to GC-MS/MS analysis was developed for quantification of caffeine, cyamemazine, meprobamate, morphine and 6-MAM in 11 biological matrices. The performance of this assay allows application in forensic toxicology or pharmacokinetic studies. The extraction protocol can be used for targeted analysis of various basic drugs and, with optimization, for other drugs or screening procedures in complex matrices. It could thus be an interesting starting set for further development for laboratories seeking to optimize their activity and confronted to analysis of new compounds or new matrices.
FORENSIC TOXICOLOGY, WITH BLT SESSION 1 O34
Castor bean self-poisoning: Report of a case with blood and urine ricinine measurements G. Hoizey (1), A. Villa (2), M. Cheze (1), J. Langrand (2), S. Mohebbi (3), A. Muckensturm (1), G. Pepin (1), M. Deveaux (1), R. Garnier (2) (1) Laboratoire Toxlab, Paris, France ; (2) Centre antipoison de Paris, hôpital Fernand Widal, Paris, France ; (3) Service de réanimation médico-chirurgicale, hôpital privé d’Antony, Antony, France. Introduction. – Ricin is a highly toxic protein from the castor bean plant (Ricinus communis) and is among the deadliest natural poisons available. We report the case of a 23 year-old man who committed suicide through both oral and intravenous self-administration of a castor bean extract. Methods. – Since it has been shown that ricin determination in clinical or post-mortem samples was difficult in real cases, ricinine, another alkaloid present in small amount in the castor bean plant, was used as a surrogate biomarker of ricin intoxication. Ricinine determination was isolated from the samples by liquid-liquid extraction and quantitatively determined by a specific LC-MS/MS method dedicated to the screening of plant toxins. MRM transitions applied for ricinine MS/MS measurement were: m/z 165 > 138 (quantification ion), 165 > 93, 165 > 84 and 165 > 82. Case Report. – A 23 year-old man was referred to the emergency department three hours after a suicidal attempt with castor bean extract. He vainly tried an intravenous self-administration of a Ricinus communis seed decoction with trimipramine, then ate twenty seeds together with 1 200 mg trimipramine (Surmontil® 4%). On admission, he was conscious and fully orientated (GCS 15). Clinical examination only revealed tachycardia (128/min); EKG disclosed no conduction or repolarization abnormalities. Blood tests were unremarkable except for a mild hypokalemia (3.4 mmol/L). Febrile diarrhea occurred 35 hours after ingestion. Lymphangitis of the left arm was also observed and blood cultures revealed Gram + cocci, when urine culture was sterile. The clinical course was transitorily complicated by: hypoglycemia (2.91 mmol/L), hyponatremia (133 mmol/L), and hyperkalemia (5.4 mmol/L) which were symptomatically compensated. Hepatic enzymes and serum creatinine were always normal. Besides symptomatic support, the patient received antibiotics and his symptoms amended, when 25 hours after admission, he escaped, threw himself out of a window, and died.
Results. – Blood and urine samples had been taken 22 hours after castor bean seed self-administration and were submitted to the laboratory for analytical assessment. Blood and urine ricinine concentrations were respectively 46 and 720 ng/mL. Conclusion. – In this case, clinical signs and symptoms were consistent with a minor ricin poisoning. However, ricinine blood and urine concentrations were high, when compared with those measured in previous case reports. In our case, as in previous reports of castor bean poisoning, ricinine levels were poorly correlated with poisoning severity. As a matter of fact, the toxic effects of the plant are mainly due to ricin which is poorly absorbed in the digestive tract. Ricinine digestive absorption is much better, but its toxicity is much lower. As a consequence, high ricinine blood and urine levels can be observed after ingestion, together with mild systemic poisoning. On the contrary, a severe poisoning may result from parenteral administration of a small amount of the plant extract with associated low serum and urine levels of ricinine. O35
Fitness to drive and cannabis: Experimental and real-life case study validation of two blood THCCOOH thresholds to distinguish occasional users from heavy smokers C. Giroud (1), M. Fabritius (1, 2), M. Augsburger (1), H. Chtioui (3), B. Favrat (1) (1) Centre universitaire romand de médecine légale, Lausanne-Geneva; (2) Institut für rechtsmedizin, university of Bern; (3) Division of clinical pharmacology, centre hospitalier universitaire vaudois, Lausanne, Switzerland. Introduction. – THC-COOH has been proposed as a criterion to help to distinguish between occasional from regular cannabis users. However, to date this indicator has not been adequately assessed under experimental and real-life conditions. Methods. – We carried out a controlled administration study of smoked cannabis with a placebo. Twenty-three heavy smokers and 25 occasional smokers, between 18 and 30 years of age, participated in this study [Battistella G et al., PloS one. 2013;8(1):e52545]. We collected data from a second real case study performed with 146 traffic offenders’ cases in which the whole blood cannabinoid concentrations and the frequency of cannabis use were known. Cannabinoid levels were determined in whole blood using tandem mass spectrometry methods. Results. – Significantly high differences in THC-COOH concentrations were found between the two groups when measured during the screening visit, prior to the smoking session, and throughout the day of the experiment. Receiver operating characteristic (ROC) curves were determined and two threshold criteria were proposed in order to distinguish between these groups: a free THC-COOH concentration below 3 μg/L suggested an occasional consumption (≤ 1 joint/week) while a concentration higher than 40 μg/L corresponded to a heavy use (≥ 10 joints/month). These thresholds were successfully tested with the second real case study. The two thresholds were not challenged by the presence of ethanol (40% of cases) and of other therapeutic and illegal drugs (24%). These thresholds were also found to be consistent with previously published experimental data. Conclusion. – We propose the following procedure that can be very useful in the Swiss context but also in other countries with similar traffic policies: If the whole blood THC-COOH concentration is higher than 40 μg/L, traffic offenders must be directed first and foremost toward medical assessment of their fitness to drive. This evaluation is not recommended if the THC-COOH concentration is lower than 3 μg/L. A THC-COOH level between these two thresholds can’t be reliably interpreted. In such a case, further medical assessment and follow up of the fitness to drive are also suggested, but with lower priority.