Liquid chromatography-tandem mass spectrometry method for determination of the pyridinium aldoxime 4-PAO in brain, liver, lung, and kidney.
A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was validated and applied to the in vitro determination of 4-[(hydroxyimino)methyl]-1-octylpyridinium cation (4-PAO), which can penetrate the blood-brain barrier and reactivate acetylcholinesterase (AChE) inhibited by alkylphosphonate in the brain, liver, lung, and kidney. The limit of detection (LOD) was 0.235 microg cation/g wet weight, and the quantification range and linearity of the calibration curve extended over a range of 0.470-941 microg cation/g wet weight. For the proof of applicability, when 4-PAO was administrated intravenously via the rat tail vein at 10% LD(50), we were able to quantify the 4-PAO concentration in the tissues: brain 7.60+/-1.32 microg cation/g wet weight (mean+/-SD, n=5), liver 26.8+/-2.82 microg cation/g, lung 76.4+/-24.9mugcation/g, and kidney 638+/-266 microg cation/g. In addition, the methods for 4-[(hydroxyimino)methyl]-1-decylpyridinium bromide (4-PAD) and 4-[(hydroxyimino)methyl]-1-(2-phenylethyl) pyridinium bromide (4-PAPE) were partly validated referring to the findings of the 4-PAO full validation. Thus, the LC-MS/MS method described in this study can be useful for quantification of pyridinium aldoxime methiodide (PAM)-type oximes in biological samples.
Sakurada
Koichi
K
National Research Institute of Police Science, 6-3-1 Kashiwanoha, Kashiwa, Chiba 277-0882, Japan. sakurada@nrips.go.jp
Ohta
Hikoto
H
D000818:Animals; D001923:Brain Chemistry; D002801:Cholinesterase Reactivators / Q000032:analysis* / Q000493:pharmacokinetics; D002853:Chromatography, Liquid / Q000379:methods*; D007668:Kidney / Q000737:chemistry; D016014:Linear Models; D008099:Liver / Q000737:chemistry; D008168:Lung / Q000737:chemistry; D008297:Male; D010091:Oximes / Q000032:analysis / Q000493:pharmacokinetics; D011220:Pralidoxime Compounds / Q000032:analysis / Q000493:pharmacokinetics; D011726:Pyridinium Compounds / Q000032:analysis / Q000737:chemistry* / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods*; D014018:Tissue Distribution
C551225:4-((hydroxyimino)methyl)-1-octylpyridinium cation; D002801:Cholinesterase Reactivators; D010091:Oximes; D011220:Pralidoxime Compounds; D011726:Pyridinium Compounds