title: Determination of deltamethrin in rat plasma and brain using gas chromatography-negative chemical ionization mass spectrometry.
abstract: Quantification of the pyrethroid deltamethrin (DLM) in small (100 μL) biological samples from rodents is essential for toxicokinetic studies of trace levels of the insecticide in foods. Such empirical kinetic data are necessary for construction of valid physiologically-based toxicokinetic models. There are no validated methods in the literature for determining deltamethrin in 100 μL plasma and brain samples. Plasma and brain samples were stabilized using sodium fluoride as an esterase inhibitor, and the DLM was extracted by protein precipitation using acetonitrile and phosphoric acid. The samples were vortexed, centrifuged, evaporated to dryness, and reconstituted in toluene prior to injection into a gas chromatograph equipped with a quadrupole mass analyzer. Samples were ionized via electron capture in the negative ion mode using methane, and the molecular ion and fragment ions of DLM were monitored using Selected-Ion Monitoring (SIM) for quantitation and verification of the analyte. Cis-permethrin was used as the internal standard for the method, which was validated according to current US FDA guidelines. Linearity was determined between 0.3 and 1,000 ng/mL, with a limit of detection of 150 pg/mL. The intra- and inter-batch variation for precision (as % relative standard deviation, RSD) and accuracy (as % bias) of the method were better than 20% at the limit of quantitation and better than 15% across the remaining linear range (n=18), with recoveries of 113% and 68% for plasma and brain respectively. Benchtop stability, autosampler stability, and freeze/thaw stability studies of the method (over a 3-day freeze/thaw cycle) were found to be within the acceptance criteria of 20% RSD and bias. This optimized method was applied to the quantitation of DLM in plasma and brain homogenate samples obtained up to 12h after oral dosing of Sprague-Dawley rats with 1mg DLM/kg body weight.
authors.affiliation: Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia, Athens, GA, United States. Electronic address: drg@uga.edu.
authors.forename: Darren
authors.initials: D
authors.lastname: Gullick
authors.affiliation: Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia, Athens, GA, United States.
authors.forename: Andrew
authors.initials: A
authors.lastname: Popovici
authors.affiliation: Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia, Athens, GA, United States.
authors.forename: Holly C
authors.initials: HC
authors.lastname: Young
authors.affiliation: Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia, Athens, GA, United States.
authors.forename: James V
authors.initials: JV
authors.lastname: Bruckner
authors.affiliation: Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia, Athens, GA, United States.
authors.forename: Brian S
authors.initials: BS
authors.lastname: Cummings
authors.affiliation: Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia, Athens, GA, United States.
authors.forename: Pei
authors.initials: P
authors.lastname: Li
authors.affiliation: Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia, Athens, GA, United States.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Bartlett
mesh_terms: D000818:Animals; D001923:Brain Chemistry / Q000502:physiology*; D004355:Drug Stability; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods*; D057230:Limit of Detection; D016014:Linear Models; D008297:Male; D009570:Nitriles / Q000032:analysis* / Q000097:blood* / Q000737:chemistry; D011722:Pyrethrins / Q000032:analysis* / Q000097:blood* / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D052616:Solid Phase Extraction; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods
chemical_list: D009570:Nitriles; D011722:Pyrethrins; C017180:decamethrin
keywords: Bioanalytical method validation; Brain homogenate; Deltamethrin; Neurotoxicity; Plasma; Pyrethroids