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Trace level quantification of deuterated 17β‐estradiol and estrone in ovariectomized mouse plasma and brain using liquid chromatography/tandem mass spectrometry following dansylation reaction
Author(s) -
Xia YuanQing,
Chang Steve W.,
Patel Shefali,
Bakhtiar Ray,
Karanam Bindhu,
Evans David C.
Publication year - 2004
Publication title -
rapid communications in mass spectrometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.528
H-Index - 136
eISSN - 1097-0231
pISSN - 0951-4198
DOI - 10.1002/rcm.1530
Subject(s) - chemistry , estrone , chromatography , metabolite , ovariectomized rat , cmax , mass spectrometry , liquid chromatography–mass spectrometry , tandem mass spectrometry , high performance liquid chromatography , pharmacokinetics , hormone , medicine , biochemistry
A sensitive liquid chromatography/tandem mass spectrometry (LC/MS/MS) method coupled with dansylation was developed for the simultaneous quantification of exogenously administered deuterated 17 β ‐estradiol‐d 4 (E2‐d 4 ) and its metabolite, estrone‐d 4 (E1‐d 4 ), in mouse plasma and brain homogenates. The dansylation reaction was simple, fast, and sensitive, and a lower limit of quantification of 50 pg/mL was achieved by using 50 μL of mouse plasma. Interference from endogenous 17 β ‐estradiol and estrone in plasma and brain samples was minimized by the use of deuterated‐E2 as well by utilizing ovariectomized (OVX) mice. The recovery of dansylated derivative exceeded 83% and the reaction was completed within approximately 3 min. The intra‐ and inter‐day assay precision were better than 12.9% and assay accuracy ranged between 92–104% for E1‐d 4 and E2‐d 4 in plasma, respectively. The absorption of E2‐d 4 at both 1 and 3 mg/kg P.O. was rapid, reaching peak plasma concentrations (C max ) at 5 min post‐dose that was the earliest time point obtained, and were 1.1 and 13.8 ng/mL, respectively; the C max values for the estrone metabolite, E1‐d 4 , were 1.1 and 43.2 ng/mL, respectively. The area‐under‐the‐plasma‐time curve (AUC 0‐2h ) values were determined to be 0.65 and 2.90 ng · h/mL for E2‐d 4 and 0.77 and 6.74 ng · h/mL for E1‐d 4 , respectively, at 1 and 3 mg/kg. The mean brain‐to‐plasma ratio for E1‐d 4 and E2‐d 4 after P.O. administration of E2‐d 4 to the OVX mice at 1 and 3 mg/kg indicated that both E1‐d 4 and E2‐d 4 were present in the brain as well as in the circulation. Copyright © 2004 John Wiley & Sons, Ltd.