Determination using liquid-chromatography-electrospray tandem mass spectroscopy of ethinylestradiol serum pharmacokinetics in adult Sprague-Dawley rats.
The pharmacokinetics of ethinylestradiol (EE2), a potent synthetic estrogen, was investigated in male and female Sprague-Dawley rats as part of a series of endocrine-active compounds, including genistein and nonylphenol. A method based on solid-phase extraction and LC with negative ion electrospray tandem mass spectrometric detection was developed and validated. The limit of detection in untreated rat serum was below 0.01 ng/ml (0.03 nM), the limit of quantification was 0.03 ng/ml (0.10 nM), the intra- and inter-day precision was 2-9%, and the intra- and inter-day accuracy was 89-94%. This method was used to determine the serum pharmacokinetics of EE2 in rats following oral gavage administration of 1 mg/kg body weight. EE2 was present in serum primarily in the unconjugated form at concentrations below 0.5 ng/ml. The maximal serum concentration was proportional to dose over the range of 0.04-0.5 mg/kg body weight and pharmacokinetic parameters were determined using model-independent analysis. Significant sex differences were observed for elimination half-times and volumes of distribution, but not for total serum clearance or maximal concentrations. The pharmacokinetic analysis of EE2 will be useful for comparing the toxicological effects of EE2 to those of other environmental estrogens in related rodent endocrine disruptor studies.
Twaddle
Nathan C
NC
Division of Biochemical Toxicology, National Center for Toxicological Research, Jefferson, AR 72079, USA.
Churchwell
Mona I
MI
Newbold
Retha R
RR
Delclos
K Barry
KB
Doerge
Daniel R
DR
D000818:Animals; D002853:Chromatography, Liquid / Q000379:methods*; D004997:Ethinyl Estradiol / Q000097:blood* / Q000493:pharmacokinetics; D005260:Female; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*
D004997:Ethinyl Estradiol