A fieldable, high-throughput, cost-efficient high performance liquid chromatography-ultraviolet absorption detection (HPLC-UV) method for the quantitation of bispyridinium quaternary aldoxime cholinesterase reactivators in blood

• Autorzy: Karvaly Gellért Balázs , Tekes Kornélia , Zoltán Szimrók , Fűrész József , Kuca Kamil , Kalás Huba

Identyfikatory

DOI

10.1556/1326.2020.00781

• Języki publikacji: EN

Abstrakty

EN

Mono- and bis-pyridinium quaternary aldoximes (K-oximes) have long been employed as cholinesterase reactivator components of antidotes against lethal cholinesterase-inhibiting organophosphorous chemicals. Their positive charge poses difficulties in their chromatographic analysis, resulting in the publication of different approaches for each K-oxime. A multiplexed method is presented for the rapid quantitation of 10 K-oximes in blood with its utility demonstrated in vivo. Liquid chromatography with absorbance detection was employed. Reversed-phase separation was achieved on a highly nonpolar stationary phase. Method validation was based on the respective guideline of the European Medicines Agency. Times to peak concentrations and 120-min areas under the time–concentration curves were determined in rats following intraperitoneal administration. Adequate retention and separation of K-oximes with acceptable peak shapes in short isocratic runs was achieved by adjusting ionic strength, organic content and the concentration of the ion-pairing agent of the mobile phase. Chromatographic properties were governed by optimizing the concentration of dissolved ions. Accurate adjustment of the organic content was indispensable for avoiding peak drifting and splitting. Dose-adjusted exposure to K-347 and K-868 was exceptionally low, while exposure to K-48 was the highest. The method is suitable for screening systemic exposure to various K-oximes and can be extended.

Słowa kluczowe

EN

pralidoxime; obidoxime; cholinesterase; cholinesterase reactivator; nerve agent

• Wydawca: University of Silesia in Katowice ; Akademiai Kiado
• Czasopismo: Acta Chromatographica
• Rocznik: 2021
• Tom: Vol. 33, no. 2
• Strony: 134--144
• Opis fizyczny: Bibliogr. 28 poz., rys., tab.

Twórcy

autor

Karvaly Gellért Balázs

• Department of Laboratory Medicine, Semmelweis University, 4 Nagyvárad tér, Budapest, H-1089, Hungary

• https://orcid.org/0000-0003-2468-5633

autor

Tekes Kornélia

• Department of Pharmacodynamics, Semmelweis University, 4 Nagyvárad tér, Budapest, H-1089, Hungary

autor

Zoltán Szimrók

• Department of Pharmacology and Pharmacotherapy, Semmelweis University, 4 Nagyvárad tér, Budapest, H-1089, Hungary

autor

Fűrész József

• Department of Laboratory Medicine, Semmelweis University, 4 Nagyvárad tér, Budapest, H-1089, Hungary

autor

Kuca Kamil

• Department of Chemistry, Faculty of Science, University of Hradec Kralove, Rokitanského 62, Hradec Králové, 500 03, Czech Republic

autor

Kalás Huba

• Department of Pharmacology and Pharmacotherapy, Semmelweis University, 4 Nagyvárad tér, Budapest, H-1089, Hungary

Bibliografia

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Uwagi

Opracowanie rekordu ze środków MNiSW, umowa Nr 461252 w ramach programu "Społeczna odpowiedzialność nauki" - moduł: Popularyzacja nauki i promocja sportu (2021).