Determination of deltamethrin and its metabolite 3-phenoxybenzoic acid in male rat plasma by high-performance liquid chromatography

The pyrethroid insecticide-deltamethrin [(S)-alpha-cyano-3-phenoxybenzyl-(IR)-cis-3-(2,2-dibromovinyl)-2,2-dimethylcyclopropane carboxylate] is widely used throughout the world in agricultural applications. It is also used to treat humans, thereby creating a possible public health concern. The toxic effects of deltamethrin in mammals include choreoathetosis, hyperexcitability and salivation. The principal mechanisms of metabolism for deltamethrin are ester hydrolysis and oxidation at the 4' position of the terminal aromatic ring. Few studies have been conducted on the toxicokinetics of deltamethrin or its metabolites, mainly due to the lack of quick, sensitive, and validated analytical methods. In this study, we describe the first method to simultaneously determine deltamethrin and its major metabolite 3-phenoxybenzoic acid (3-PBAcid). This method utilizes protein precipitation and high-performance liquid chromatography to support a toxicokinetic study in the rat. The limit of quantitation for both deltamethrin and 3-PBAcid was 0.1 mug/ml. The recoveries for deltamethrin and 3-PBAcid were approximately 91 and 94%, respectively. Intra-day (n = 5) precision (relative standard deviation, %R.S.D.) and accuracy (%Error) for deltamethrin ranged from 1.5 to 12.3% and from 4.0 to 10.6%, respectively. The inter-day (n = 15) precision (%R.S.D.) and accuracy (%Error) for deltamethrin ranged from 7.1 to 11.6% and from 6.3 to 8.2%, respectively. Intra-day (n = 5) precision (%R.S.D.) and accuracy (%Error) for 3-PBAcid ranged from 1.7 to 13.1 % and from 1.3 to 14.5%, respectively. The inter-day (n = 15) precision (%R.S.D.) and accuracy (%Error) for 3-PBAcid ranged from 5.4 to 14.5% and from 5.1 to 12.8%, respectively. Finally, this method was applied to a toxicokinetic study of deltamethrin in the rat. (C) 2004 Elsevier B.V. All rights reserved.