A novel high‐performance liquid chromatography with diode array detector method for the simultaneous quantification of the enzyme‐reactivating oximes obidoxime, pralidoxime, and HI‐6 in human plasma

Kranawetvogl, Tamara; Steinritz, Dirk; Thiermann, Horst; John, Harald

doi:10.1002/dta.2800

Cited by 8 publications

(5 citation statements)

References 55 publications

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“…In addition, Asoxime Chloride (HI-6) is a substantially broad-spectrum AChE reactivator, and a double-positive charged bispyridinium compound, commonly used in Canada, Sweden, and the Czech Republic. It has shown acceptable effects in treating Sarin, VX, Soman and cyclosarin ( Kassa et al, 2007 ; Cuya et al, 2018 ; Whitmore et al, 2018 ; Kranawetvogl et al, 2020 ). Timedoxime bromide, or TMB4, is another oxime that is particularly successful in regenerating AChE, although its use is restricted due to liver and CNS side effects ( SZ et al, 1985 ).…”

Section: Methodsmentioning

confidence: 99%

“…Based on a study by Kovarik and Macek in 2020, coordinated stereoselective preference for the OP enantiomer for inactivation and reactivation is a benefit of cholinesterase as a bioscavenger (Kovarik and Hrvat, 2020). Kranawetvogl et al, in 2020, introduced a new, simple, and rugged HPLC-DAD (High-Performance Liquid Chromatography with Diode-Array Detection) technique, which is functional for the single analysis of Obidoxime, 2-PAM, and HI-6 in human plasma by using 4-pyridinealdoxime as the internal standard and sensitive DAD detection. Their study focused on fulfilling a successful approach to improving therapies involving the combined administration of different oximes (Kranawetvogl et al, 2020).…”

Section: Successful Advanced Therapiesmentioning

confidence: 99%

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A complete, evidence-based review on novichok poisoning based on epidemiological aspects and clinical management

et al. 2023

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Background: The whole world has learned about the existence of a highly toxic neuro-paralytic substance called Novichok. A wide range of neuro-paralytic toxins were used during the wars of decades ago, which also had harmful and irreversible effects. Fortunately, the establishment of conventions prohibiting the use of these weapons prevented the adverse clinical consequences of these compounds. What we did in the present study was to evaluate the clinical features of Novichok, how to manage exposure to it, and to evaluate the prognostic aspects associated with this poisoning agent.Methods: The manuscript especial databases including Medline, Web of knowledge, Google scholar, and Scopus were deeply searched by the two blinded investigators for all eligible studies based on the considered keywords. Initially 98 articles were initially collected by database searching that considering eligibility criteria, 83 articles were finally eligible for the final assessment. There is a lack of clinical trials and case-cohort studies on general population about treatment and side effects when it comes to human nerve agents and most of the data in our search is based on animal studies.Results: In evaluating various clinical, auto physiological and prognostic aspects of exposure to these substances, special attention was necessary to the following points. First, Novichok agents are considered more potent than other toxic agents. Pathophysiologically, these agents irreversibly bind acetylcholinesterase and produce a rapid cholinergic toxidrome which is responsible for the clinical manifestations as well as the potential dangerous and life threatening side effects caused by these agents. Uniquely, these agents are thought to also target every neuron in the central and peripheral nervous system. As a managerial and therapeutic approach, early and timely treatment of its related complication along with prevents massive exposure and decontamination in addition to rapid resuscitation can prohibit debilitating neuropathy and death due to facing it.Conclusion: The present review highlights the importance of recognizing the potential acute toxic effects of Novichok agents, diagnostic and therapeutic approaches (life-saving antidotal therapy) to complications and ultimately the application of guidelines to improve the prognosis of exposure to these agents for both victims and medical community.

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Section: Methodsmentioning

confidence: 99%

Section: Successful Advanced Therapiesmentioning

confidence: 99%

A complete, evidence-based review on novichok poisoning based on epidemiological aspects and clinical management

et al. 2023

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“…In addition to the oximes mentioned above, asoxime chloride (HI-6) restores the activity of AChE inhibited by OP [ 21 ]. This double positive charged bis-pyridinium compound has been shown to be effective in the treatment of neural factors [ 48 , 49 ]. A bis-pyridinium oxime with superior therapeutic and pharmaceutical properties compared to both obidoxime and 2-PAM is a methoxime (MMB-4) [ 50 ].…”

Section: Treatment Of Novichok Exposure: Where To Start?mentioning

confidence: 99%

Review of Possible Therapies in Treatment of Novichoks Poisoning and HAZMAT/CBRNE Approaches: State of the Art

Noga¹,

Michalska²,

Jurowski

2023

JCM

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Novichoks-organophosphorus compounds belong to the nerve agents group, constituting the fourth generation of chemical warfare agents. The tremendous toxicity of Novichoks is assumed to be several times greater than that of VX, whereas no published experimental research supports this. They were surreptitiously created during the Cold War by the Soviet Union. Novichok’s toxic action mechanism consists of the inhibition of acetylcholinesterase activity. The review includes data on treating poisoning caused by OPs which could be used as guidelines for the therapy in case of Novichok exposure and HAZMAT/CBRNE approaches. Novichoks pose a severe threat due to their toxicity; however, there is insufficient information about the identity of A-series nerve agents. Filling in the missing data gaps will accelerate progress in improving protection against Novichoks and developing optimal therapy for treating poisoning casualties. Furthermore, introducing solutions to protect medical personnel in contact with a hazardous substance increases the chances of saving casualties of HAZMAT/CBRNE incidents.

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“…Obidoxime was measured via reversed-phase ion-pair chromatography-diode array detection (RPIPC-DAD) as described recently (Kranawetvogl et al, 2020). Atropine was monitored by LC-ESI MS/MS in multiple reaction monitoring mode (John et al, 2010b).…”

Section: Determination Of Antidotes Obidoxime and Atropinementioning

confidence: 99%

A case report of severe pirimiphos-methyl intoxication: Clinical findings and cholinesterase status

et al. 2022

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A 63-year-old male was admitted to a district hospital after ingesting ethanol and pirimiphos-methyl (PM) with suicidal intentions. History included alcoholic cirrhosis with alcoholism, adiposity, diabetes with cerebral microangiopathy, chronic renal insufficiency, heparin-induced thrombocytopenia, and status post necrotizing fasciitis. Emergency medical service reported an alert patient without signs of cholinergic crisis; activated charcoal and atropine were administered. Upon hospital arrival, he received fluid resuscitation, activated charcoal, and atropine. He was transferred to a toxicology unit the next day. On admission, he had no cholinergic signs (dry mucous membranes, warm skin, and mydriatic pupils) requiring small atropine doses (0.5 mg per hour). Four hours after admission, he developed bradycardia and respiratory distress, necessitating intubation. He received atropine by continuous infusion for 7 days (248 mg total) and obidoxime (bolus and continuous infusion). PM, pirimiphos-methyl-oxon (PMO), and phosphorylated tyrosine (Tyr) adducts derived from human serum albumin were analyzed in vivo. Cholinesterase status (acetylcholinesterase (AChE), butyrylcholinesterase (BChE), inhibitory activity of patient plasma and reactivatability, and phosphorylated BChE-derived nonapeptides) was measured in vivo. Obidoxime and atropine were monitored. PM and PMO were detectable, PM with maximum concentration ∼24 h post admission (p.a.) and PMO at ∼18 h p.a. Tyr adducts were detectable. AChE in vivo was suppressed on admission, increased continuously after starting obidoxime, and reached maximum activity after ∼30 h. AChE in vivo and reactivatability remained at the same level until the end of monitoring. BChE was already suppressed on admission; termination of the antidote treatment was possible after BChE had recovered to 1/5th of its normal value and extubation was possible after BChE had recovered to 2/5th. While a substantial part of BChE was already aged on admission, aging continued peaking at ∼24 h p.a. After initiating obidoxime treatment, plasma levels increased until obidoxime plasma levels reached a steady state. On admission, plasma atropine level was low; it increased with the start of the continuous infusion. Afterward, the level dropped to a steady state. The clinical course was characterized by bouts of pneumonia, necessitating re-intubation and prolonged ventilation, sepsis, delirium, and a peripheral neuropathy. After psychiatric evaluation, the patient was discharged to a neurological rehabilitation facility after 77 days of hospital care.

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A novel high‐performance liquid chromatography with diode array detector method for the simultaneous quantification of the enzyme‐reactivating oximes obidoxime, pralidoxime, and HI‐6 in human plasma

Cited by 8 publications

References 55 publications

A complete, evidence-based review on novichok poisoning based on epidemiological aspects and clinical management

A complete, evidence-based review on novichok poisoning based on epidemiological aspects and clinical management

Review of Possible Therapies in Treatment of Novichoks Poisoning and HAZMAT/CBRNE Approaches: State of the Art

A case report of severe pirimiphos-methyl intoxication: Clinical findings and cholinesterase status

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