A liquid chromatographic–mass spectrometric (LC–MS) method for the analysis of the bis-pyridinium oxime ICD-585 in plasma: Application in a guinea pig model

Capacio, Benedict R.; Dusick, B.; Smith, J. Richard; McDonough, John H.; Shih, Tsung‐Ming

doi:10.1016/j.jchromb.2009.12.011

Cited by 6 publications

(2 citation statements)

References 9 publications

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“…Similar U or V shaped retention profiles have been observed under the zwitterionic HILIC separation mechanism [21]. The assay of oximes in biological matrices is often based on the RP separation mechanism [13,14,16,22,23]. Gradient elution based on the combination between aqueous volatile buffer solutions (i.e., ammonium formate and acetate) and organic modifiers (acetonitrile, methanol or their mixtures) is more often preferred.…”

mentioning

confidence: 82%

LC–MS/MS Approaches for The Assay of Bis -Quaternary Pyridinium Oximes Used as Ache Reactivators in Biological Matrices

Voicu

Albu²,

Tache

et al. 2013

Bioanalysis

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confidence: 82%

LC–MS/MS Approaches for The Assay of Bis -Quaternary Pyridinium Oximes Used as Ache Reactivators in Biological Matrices

Voicu

Albu²,

Tache

et al. 2013

Bioanalysis

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“…None of the RP‐ and IP‐ chromatographic methods described above was used for absolute quantification of POX so far and consequently no procedure has been validated for this use. In contrast, validated procedures for the measurement of related oximes are used in clinical trials and for pharmacokinetic studies underlining the reliability of such methods 42–45…”

Section: Chromatographic Analysis Of Phosphylated Oximesmentioning

confidence: 99%

Chromatographic analysis of toxic phosphylated oximes (POX): a brief overview

Becker¹,

Worek²,

John³

2010

Drug Testing and Analysis

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Poisoning with organophosphorus compounds (OP), e.g. pesticides and nerve agents, causes inhibition of acetylcholinesterase (AChE) by phosphylation of the active site serine residue. Consequently, accumulation of stimulating acetylcholine in the synaptic cleft induces cholinergic crisis which ultimately may lead to death. For standard causal therapy, enzyme reactivators are administered representing oxime derivatives of quarternary pyridinium compounds, e.g. pralidoxime (2-PAM), obidoxime and HI 6. The mechanism of action includes removal of the phosphyl moiety by a nucleophilic attack of the oximate molecule substituting the enzyme and forming a phosphylated oxime (POX). POX is produced in stoichiometric amounts of reactivated enzyme and exhibits a significantly enhanced toxicity (inhibition rate constant) when compared to the parent OP. However, stability of POX under physiological conditions appears to be highly limited. Nevertheless, the presence of POX reveals a potential critical issue for both therapeutic efficacy in vivo and pharmacokinetic and pharmacodynamic (PK-PD) modelling based on cholinesterase activity data. Detailed characterization represents an important need for elaboration of the entire oxime pharmacology.Nevertheless, reports on POX toxicity and analysis are quite rare and may therefore be indicative of the challenge of POX analysis. This review provides a concise overview of chromatographic approaches applied to POX separation. Chromatography represents the key technology for POX purification and quantification in kinetic in vitro studies using buffers and biological fluids. Applications based on reversed-phase chromatography (RPC), ion pair chromatography (IPC) and an affinity approach as well as thin layer chromatography (TLC) are discussed and novel applications and data are presented.

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Current literature in mass spectrometry

2010

J. Mass Spectrom.

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A liquid chromatographic–mass spectrometric (LC–MS) method for the analysis of the bis-pyridinium oxime ICD-585 in plasma: Application in a guinea pig model

Cited by 6 publications

References 9 publications

LC–MS/MS Approaches for The Assay of Bis -Quaternary Pyridinium Oximes Used as Ache Reactivators in Biological Matrices

LC–MS/MS Approaches for The Assay of Bis -Quaternary Pyridinium Oximes Used as Ache Reactivators in Biological Matrices

Chromatographic analysis of toxic phosphylated oximes (POX): a brief overview

Current literature in mass spectrometry

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