title: An HPLC method for the simultaneous determination of neurotoxic dipyridyl isomers in human plasma.
abstract: Several studies on dipyridyl isomers have suggested that they are neurotoxic and that chronic exposure to these compounds could be a potential human health hazard. A reversed phase HPLC method was developed for the simultaneous quantitation of 2,2'-dipyridyl and its four positional isomers, 2,3'-, 2,4'-, 3,4'- and 4,4'-dipyridyl in human plasma. Plasma samples were basified, extracted with 1-chlorobutane, evaporated, the residue reconstituted in mobile phase, and an aliquot part was analyzed by HPLC. Chromatographic separations were performed on a C(18) reversed phase Sunfire column eluted with a mobile phase composed of potassium phosphate (pH 3.5; 25 mM)-acetonitrile (80:20, v/v). Isomers were separated with good resolution, and quantification was determined utilizing an internal standard of quinoxaline. The method has been validated over a range from 30 to 2000 ng/ml with correlation coefficients higher than 0.995. Extraction recoveries for the dipyridyl isomers averaged from 65 to 92%. Limit of detection and limit of quantitation for the dipyridyl isomers ranged from 15 to 70 ng/ml and 30 to 90 ng/ml, respectively. The inter- and intra-day variation did not exceed 7% with an accuracy range of 96-102%. The described analytical method was successfully utilized for the determination of dipyridyl isomers in human plasma and suggested the need for more routine monitoring of tobacco smokers and other individuals who are involuntarily exposed to environmental source of dipyridyl isomers.
authors: Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536, USA.
authors: Ahmad H
authors: AH
authors: Malkawi
authors: Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536, USA.
authors: Abeer M
authors: AM
authors: Al-Ghananeem
authors: Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536, USA.
authors: Shama
authors: S
authors: Nasim
authors: University of Kentucky Mental Health Research Center at Eastern State Hospital, Lexington, KY 40508, USA.
authors: Jose
authors: J
authors: de Leon
authors: Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536, USA. Electronic address: pcrooks@email.uky.edu.
authors: Peter A
authors: PA
authors: Crooks
mesh_terms: D015082:2,2'-Dipyridyl / Q000737:chemistry / Q000302:isolation & purification*; D002138:Calibration; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004355:Drug Stability; D004785:Environmental Pollutants / Q000097:blood* / Q000737:chemistry; D006801:Humans; D007536:Isomerism; D015394:Molecular Structure; D020258:Neurotoxicity Syndromes / Q000097:blood*; D012015:Reference Standards; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D012907:Smoking / Q000097:blood
chemical_list: D004785:Environmental Pollutants; D015082:2,2'-Dipyridyl