title: High-performance liquid chromatographic determination of the plasma concentration of K-27, a novel oxime-type cholinesterase reactivator.
abstract: A simple and reliable HPLC method for the determination of the plasma level of K-27, an oxime type antidote of use in organophosphorus poisoning is presented. Separation was carried out by HPLC using an octyl silica stationary phase and a mobile phase consisting of 93% phosphate buffer (pH 2.6) containing octane sulfate sodium salt, and 7% methanol. Quantitative absorbance was monitored at 286 nm. The calibration curve was linear through the range of 1.25-200 microg/mL, that is well beyond the detected plasma level range of K-27. Limit of quantitation was 5 microg/mL. Intra-day and inter-day precisions of the HPLC determinations gave standard deviations as 0.77 and 2.67%, respectively. Following intramuscular administration of 50 micromol (22.31 mg) K-27 in rats, the maximum of K-27 concentration in plasma was reached at about 15 min giving 186 microg/mL and the t(1/2) was 85 min. K-27 displays initial (from 15 trough 120 min) zero order elimination kinetics. Similar results have been found after intraperitoneal administration.
authors.affiliation: Department of Pharmacodynamics, Semmelweis University, Budapest, Hungary.
authors.forename: K
authors.initials: K
authors.lastname: Tekes
authors.forename: M Y
authors.initials: MY
authors.lastname: Hasan
authors.forename: R
authors.initials: R
authors.lastname: Sheen
authors.forename: K
authors.initials: K
authors.lastname: Kuca
authors.forename: G
authors.initials: G
authors.lastname: Petroianu
authors.forename: K
authors.initials: K
authors.lastname: Ludányi
authors.forename: H
authors.initials: H
authors.lastname: Kalász
mesh_terms: D000818:Animals; D002138:Calibration; D002801:Cholinesterase Reactivators / Q000097:blood* / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D005260:Female; D013058:Mass Spectrometry / Q000379:methods; D015394:Molecular Structure; D010091:Oximes / Q000097:blood* / Q000737:chemistry; D011726:Pyridinium Compounds / Q000097:blood* / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D015203:Reproducibility of Results
chemical_list: C513728:4-(aminocarbonyl)-1-(3-(4-((E)-(hydroxyimino)methyl)pyridinium-1-yl)propyl)pyridinium dibromide; D002801:Cholinesterase Reactivators; D010091:Oximes; D011726:Pyridinium Compounds