| Trace LC/MS/MS quantitation of 17beta-estradiol as a biomarker for selective estrogen receptor modulator activity in the rat brain. | |
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MedLine Citation:
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PMID: 19882750 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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A sensitive LC/MS/MS method has been developed by derivatization of 17beta-estradiol (E2) with dansyl chloride to quantitate 17beta-E2 in female rat serum. The use of E2-d(5) minimized interferences from endogenous 17beta-E2 in order to achieve a limit of quantitation (LOQ) of 2.5 pg/ml using 150 microl 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 17beta-E2 occurred for rats dosed with SERMs that are known to penetrate the brain and disrupt the hypothalamic-pituitary-ovarian (HPO) axis. Variations in 17beta-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. |
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Authors:
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Chris Petucci; Tom Lloyd; Heather A Harris; Xiaochun Zhang; Vargheese M Chennathukuzhi; Belew Mekonnen; Yanxuan Cai |
Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Journal of mass spectrometry : JMS Volume: 45 ISSN: 1096-9888 ISO Abbreviation: J Mass Spectrom Publication Date: 2010 Jan |
Date Detail:
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Created Date: 2010-01-11 Completed Date: 2010-03-10 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9504818 Medline TA: J Mass Spectrom Country: England |
Other Details:
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Languages: eng Pagination: 65-71 Citation Subset: IM |
Copyright Information:
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Copyright 2009 John Wiley & Sons, Ltd. |
Affiliation:
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Discovery Analytical Chemistry, Pfizer, Collegeville, PA 19426, USA. cmpetucci@verizon.net |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Biological Markers / blood* Brain Chemistry* Chromatography, Liquid / methods* Drug Stability Estradiol / blood* Female Radioimmunoassay Rats Rats, Sprague-Dawley Reproducibility of Results Selective Estrogen Receptor Modulators / metabolism* Sensitivity and Specificity Steroid 17-alpha-Hydroxylase / metabolism Tandem Mass Spectrometry / methods* |
| Chemical | |
Reg. No./Substance:
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0/Biological Markers; 0/Selective Estrogen Receptor Modulators; 50-28-2/Estradiol; EC 1.14.99.9/Steroid 17-alpha-Hydroxylase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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