Analysis of a Ricin Biomarker, Ricinine, in 989 Individual Human Urine Samples

Pittman, Christopher T.; Guido, John M.; Hamelin, Elizabeth I.; Blake, Thomas A.; Johnson, Rudolph C.

doi:10.1093/jat/bkt010

Cited by 20 publications

(9 citation statements)

References 19 publications

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“…Ricinine may only serve as a surrogate marker or indicator of ricin intoxication, as the ricin toxin is not actually being detected. Additionally, ricinine is expected to be present in the general population, with a recovery rate of 1.2% in persons who were not suspected of ricin exposure . Currently, there are no reports of human ricinine poisonings.…”

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confidence: 99%

Ultrasensitive Detection of Ricin Toxin in Multiple Sample Matrixes Using Single-Domain Antibodies

et al. 2015

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Ricin is an extremely potent ribosomal inactivating protein listed as a Category B select agent. Although ricin intoxication is not transmittable from person to person, even a single ricin molecule can lead to cell necrosis because it inactivates 1500 ribosomes/min. Since there is currently no vaccine or therapeutic treatment for ricin intoxication, ultrasensitive analytical assays capable of detecting ricin in a variety of matrixes are urgently needed to limit exposure to individuals as well as communities. In this paper, we present the development and application of a single-molecule array (Simoa) for the detection of ricin toxin in human urine and serum. Single-domain antibodies (sdAbs), among the smallest engineered binding fragments, were chemically coupled to the surface of paramagnetic beads for the sensitive detection of ricin toxin. The Simoa was able to detect ricin at levels of 10 fg/mL, 100 fg/mL, and 1 pg/mL in buffer, urine and serum, respectively, in a fraction of the assay time need using immuno-polymerase chain reaction (IPCR). Using a fully automated state-of-the-art platform, the Simoa HD-1 analyzer, the assay time was reduced to 64 min.

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confidence: 99%

Ultrasensitive Detection of Ricin Toxin in Multiple Sample Matrixes Using Single-Domain Antibodies

et al. 2015

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“…This is due to the presence of ricinine in pharmaceutical and cosmetic products containing castor oil (27). In a previous study, a larger convenience set of 989 individual urine specimens was analyzed, and ricinine was present in 1.2% of the specimens (28). The LRL for ricinine in urine and serum was determined to be fit-for-purpose at 0.300 ng/mL based on observations in unexposed convenience sets, animal studies, and previously reported exposures (13–17, 28).…”

Section: Resultsmentioning

confidence: 99%

“…In a previous study, a larger convenience set of 989 individual urine specimens was analyzed, and ricinine was present in 1.2% of the specimens (28). The LRL for ricinine in urine and serum was determined to be fit-for-purpose at 0.300 ng/mL based on observations in unexposed convenience sets, animal studies, and previously reported exposures (13–17, 28). Example chromatograms of ricinine in a representative convenience set sample as compared to the LRL are plotted in Figure 3A.…”

Section: Resultsmentioning

confidence: 99%

Quantification of Ricinine and Abrine in Human Plasma by HPLC–MS-MS: Biomarkers of Exposure to Ricin and Abrin

Isenberg

Carter

Miller

et al. 2018

Journal of Analytical Toxicology

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Ricin and abrin are toxic ribosome-inactivating proteins found in plants. Exposure to these toxins can be detected using the biomarkers ricinine and abrine, which are present in the same plant sources as the toxins. The concentration of the biomarkers in urine and blood will be dependent upon the purification of abrin or ricin, the route of exposure, and the length of time between exposure and sample collection. Here, we present the first diagnostic assay for the simultaneous quantification of both ricinine and abrine in blood matrices. Furthermore, this is the first-ever method for the detection of abrine in blood products. Samples were processed by isotope-dilution, solid-phase extraction, protein precipitation and quantification by HPLC-MS-MS. This analytical method detects abrine from 5.00 to 500 ng/mL and ricinine from 0.300 to 300 ng/mL with coefficients of determination of 0.996 ± 0.003 and 0.998 ± 0.002 (n = 22), respectively. Quality control material accuracy was determined to have <10% relative error, and precision was within 19% relative standard deviation. The assay's time-to-first result is three hours including sample preparation. Furthermore, the method was applied for the quantification of ricinine in the blood of a patient who had intentionally ingested castor beans to demonstrate the test was fit-for-purpose. This assay was designed to support the diagnosis of ricin and abrin exposures in public health investigations.

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“…Of note, however, ricinine may also be detectable in the general population since many consumer products contain castor oil. This has been shown, for example, in a study of Pittman and co-workers who characterized urinary ricinine concentrations from 989 individuals presumably unexposed to ricin (Pittman et al 2013).…”

Section: Ricin Detectionmentioning

confidence: 89%

Ricin and Ricinus communis in pharmacology and toxicology-from ancient use and “Papyrus Ebers” to modern perspectives and “poisonous plant of the year 2018”

Franke

Scholl

Aigner

2019

Naunyn-Schmiedeberg's Arch Pharmacol

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While probably originating from Africa, the plant Ricinus communis is found nowadays around the world, grown for industrial use as a source of castor oil production, wildly sprouting in many regions, or used as ornamental plant. As regards its pharmacological utility, a variety of medical purposes of selected parts of the plant, e.g., as a laxative, an anti-infective, or an antiinflammatory drug, have been described already in the sixteenth century BC in the famous Papyrus Ebers (treasured in the Library of the University of Leipzig). Quite in contrast, on the toxicological side, the native plant has become the "poisonous plant 2018" in Germany. As of today, a number of isolated components of the plant/seeds have been characterized, including, e.g., castor oil, ricin, Ricinus communis agglutinin, ricinin, nudiflorin, and several allergenic compounds. This review mainly focuses on the most toxic protein, ricin D, classified as a type 2 ribosome-inactivating protein (RIP2). Ricin is one of the most potent and lethal substances known. It has been considered as an important bioweapon (categorized as a Category B agent (second-highest priority)) and an attractive agent for bioterroristic activities. On the other hand, ricin presents great potential, e.g., as an anticancer agent or in cell-based research, and is even explored in the context of nanoparticle formulations in tumor therapy. This review provides a comprehensive overview of the pharmacology and toxicology-related body of knowledge on ricin. Toxicokinetic/toxicodynamic aspects of ricin poisoning and possibilities for analytical detection and therapeutic use are summarized as well.

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Analysis of a Ricin Biomarker, Ricinine, in 989 Individual Human Urine Samples

Cited by 20 publications

References 19 publications

Ultrasensitive Detection of Ricin Toxin in Multiple Sample Matrixes Using Single-Domain Antibodies

Ultrasensitive Detection of Ricin Toxin in Multiple Sample Matrixes Using Single-Domain Antibodies

Quantification of Ricinine and Abrine in Human Plasma by HPLC–MS-MS: Biomarkers of Exposure to Ricin and Abrin

Ricin and Ricinus communis in pharmacology and toxicology-from ancient use and “Papyrus Ebers” to modern perspectives and “poisonous plant of the year 2018”

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