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Trace LC/MS/MS quantitation of 17β-estradiol as a biomarker for selective estrogen receptor modulator activity in the rat brain
Journal of mass spectrometry., 2010, Vol.45 (1), p.65-71
Petucci, Chris
Lloyd, Tom
Harris, Heather A
Zhang, Xiaochun
Chennathukuzhi, Vargheese M
Mekonnen, Belew
Cai, Yanxuan
2010
Volltextzugriff (PDF)
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.
Sprache
Englisch
Identifikatoren
ISSN: 1076-5174
eISSN: 1096-9888
DOI: 10.1002/jms.1689
Titel-ID: cdi_crossref_primary_10_1002_jms_1689
Format
–
Schlagworte
Analytical, structural and metabolic biochemistry
,
Biological and medical sciences
,
biomarker
,
Fundamental and applied biological sciences. Psychology
,
gene expression
,
mass spectrometry
,
Other biological molecules
,
quantitation
,
Terpenes, steroids. Hormones
,
trace detection
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