Details

Autor(en) / Beteiligte

• Petucci, Chris
• Lloyd, Tom
• Harris, Heather A
• Zhang, Xiaochun
• Chennathukuzhi, Vargheese M
• Mekonnen, Belew
• Cai, Yanxuan

Titel

Trace LC/MS/MS quantitation of 17β-estradiol as a biomarker for selective estrogen receptor modulator activity in the rat brain

Ist Teil von

• Journal of mass spectrometry., 2010, Vol.45 (1), p.65-71

Ort / Verlag

Chichester, UK: John Wiley & Sons, Ltd

Erscheinungsjahr

2010

Quelle

Wiley Online Library

Beschreibungen/Notizen

• A sensitive LC/MS/MS method has been developed by derivatization of 17β-estradiol (E2) with dansyl chloride to quantitate 17β-E2 in female rat serum. The use of E2-d₅ minimized interferences from endogenous 17β-E2 in order to achieve a limit of quantitation (LOQ) of 2.5 pg/ml using 150 μl of female rat serum. The recovery of the dansyl derivative was 95% or greater in quality control samples. The intra and interday assay precision was better than 8.2 and 6.2%, respectively, with accuracies ranging from 97 to 101% in the quality control samples. The assay was used for the quantitation of serum E2 as a biomarker for the estrogen receptor (ER) antagonist activity of small molecule SERMs (selective estrogen receptor modulators) in the female rat brain. The study revealed that a statistically significant upregulation of serum 17β-E2 occurred for rats dosed with SERMs that are known to penetrate the brain and disrupt the hypothalamic-pituitary-ovarian (HPO) axis. Variations in 17β-E2 in ascending dose studies also correlated with the corresponding trends in CYP17a1 levels, an mRNA biomarker for ovarian hyperstimulation. This biomarker assay has provided a useful screen for medicinal chemistry optimization to produce SERMs that do not interfere with negative feedback of estrogens on the brain and for biological hypothesis testing. Copyright © 2009 John Wiley & Sons, Ltd.