Lethal Injection of a Castor Bean Extract: Ricinine Quantification as a Marker for Ricin Exposure Using a Validated LC-MS/MS Method.

Ricin is a highly toxic agent derived from the castor bean plant (Ricinus communis). Poisoning occurs commonly by oral ingestion of the beans. Injection of ricin is believed to be more lethal. Ricin is a large glycosylated protein difficult to detect in clinical samples. Instead, ricinine, a small alkaloid found in the same beans, is used as surrogate marker for ricin exposure. We describe a simple LC-MS/MS method for the detection of ricinine in serum, blood and urine, validated according to EMA guidelines and successfully applied to patient samples of a suicidal death after injection of a castor bean extract. A 26-year-old man self-presented to the emergency department with severe abdominal cramps and nausea after injection of a castor bean extract. Due to rapid deterioration of his hemodynamic function despite early aggressive fluid resuscitation, he was transferred to ICU. Abdominal cramps worsened and a fulminant diarrhea developed, resulting in hypovolemic shock and cardiorespiratory collapse. Despite full supportive therapy, the patient died approximately 10 hours after injection due to multiple organ failure. Ricinine was quantified by LC-MS/MS after LLE with diethyl ether using ricinine-D3 as internal standard. Six hours after injection, ricinine concentrations in serum and blood were 16.5 and 12.9 ng/mL, respectively, which decreased to 12.4 and 10.6 ng/mL, 4 hours later. The urinary concentration was 81.1 ng/mL 7 hours after injection, which amply exceeded the levels previously reported in similar cases with lethal outcome. Concentrations of ricinine, compatible with a lethal exposure to castor beans, were detected in serum, blood and urine. Ricinine was also found in bile and liver tissue.

A comprehensive LC-MS-based quantitative analysis of fentanyl-like drugs in plasma and urine.

Fentanyl, norfentanyl, alfentanil, sufentanil, remifentanil and 3-methylfentanyl are potent, short-acting, synthetic narcotic analgesics that are not revealed in standard opiate immunoassays. In this article, a fully validated analytical method for the determination of these fentanyl-type compounds in plasma and urine is presented, consisting of a liquid-liquid extraction followed by a LC-MS/MS analysis using electrospray ionisation in the positive ionisation mode. Fentanyl-d(5) and norfentanyl-d(5) were used as internal standards. The lower LOQ in plasma and urine was 0.1 ng/mL for fentanyl, norfentanyl, alfentanil, remifentanil and 3-methylfentanyl, and 0.2 ng/mL for sufentanil. The method proved linear over a concentration range of 0.2-50 ng/mL for sufentanil and 0.1-50 ng/mL for all other analytes, with correlation coefficients of 0.998 or better. The analytical procedure showed excellent selectivity and precision (all CVs below 15%) for all analytes. Accuracy was good, except for sufentanil, where deviations of more than 15% from nominal concentrations were observed. No matrix effects were observed, and stability of stock and internal standard solutions was within acceptability limits.