Abstract
Estrogens and their bioactive metabolites play key roles in regulating diverse processes in health and disease. In particular, estrogens and estrogenic metabolites have shown both protective and non-protective effects on disease pathobiology, implicating the importance of this steroid pathway in disease diagnostics and monitoring. All estrogens circulate in a wide range of concentrations, which in some patient cohorts can be extremely low. However, elevated levels of estradiol are reported in disease. For example, in pulmonary arterial hypertension (PAH) elevated levels have been reported in men and postmenopausal women. Conventional immunoassay techniques have come under scrutiny, with their selectivity, accuracy and precision coming into question. Analytical methodologies such as gas and liquid chromatography coupled to single and tandem mass spectrometric approaches (GC–MS, GC–MS/MS, LC–MS and LC–MS/MS) have been developed to quantify endogenous estrogens and in some cases their bioactive metabolites in biological fluids such as urine, serum, plasma and saliva. Liquid-liquid or solid-phase extraction approaches are favoured with derivatization remaining a necessity for detection in lower volumes of sample. The limits of quantitation of individual assays vary but are commonly in the range of 0.5–5 pg/mL for estrone and estradiol, with limits for their bioactive metabolites being higher. This review provides an overview of current approaches for measurement of unconjugated estrogens in biological matrices by MS, highlighting the advances in this field and the challenges remaining for routine use in the clinical and research environment.
| Original language | English |
|---|---|
| Article number | 105373 |
| Number of pages | 12 |
| Journal | Journal of Steroid Biochemistry and Molecular Biology |
| Volume | 192 |
| Early online date | 19 May 2019 |
| DOIs | |
| Publication status | Published - 30 Sep 2019 |
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Keywords
- bioactive metabolites
- estrogen
- disease pathobiology
- steroid pathway
- disease diagnostics
- monitoring
Cite this
}
Current strategies for quantification of estrogens in clinical research. / Denver, Nina; Khan, Shazia; Homer, Natalie Z.M.; MacLean, Margaret R.; Andrew, Ruth.
In: Journal of Steroid Biochemistry and Molecular Biology , Vol. 192, 105373, 30.09.2019.Research output: Contribution to journal › Article
TY - JOUR
T1 - Current strategies for quantification of estrogens in clinical research
AU - Denver, Nina
AU - Khan, Shazia
AU - Homer, Natalie Z.M.
AU - MacLean, Margaret R.
AU - Andrew, Ruth
PY - 2019/9/30
Y1 - 2019/9/30
N2 - Estrogens and their bioactive metabolites play key roles in regulating diverse processes in health and disease. In particular, estrogens and estrogenic metabolites have shown both protective and non-protective effects on disease pathobiology, implicating the importance of this steroid pathway in disease diagnostics and monitoring. All estrogens circulate in a wide range of concentrations, which in some patient cohorts can be extremely low. However, elevated levels of estradiol are reported in disease. For example, in pulmonary arterial hypertension (PAH) elevated levels have been reported in men and postmenopausal women. Conventional immunoassay techniques have come under scrutiny, with their selectivity, accuracy and precision coming into question. Analytical methodologies such as gas and liquid chromatography coupled to single and tandem mass spectrometric approaches (GC–MS, GC–MS/MS, LC–MS and LC–MS/MS) have been developed to quantify endogenous estrogens and in some cases their bioactive metabolites in biological fluids such as urine, serum, plasma and saliva. Liquid-liquid or solid-phase extraction approaches are favoured with derivatization remaining a necessity for detection in lower volumes of sample. The limits of quantitation of individual assays vary but are commonly in the range of 0.5–5 pg/mL for estrone and estradiol, with limits for their bioactive metabolites being higher. This review provides an overview of current approaches for measurement of unconjugated estrogens in biological matrices by MS, highlighting the advances in this field and the challenges remaining for routine use in the clinical and research environment.
AB - Estrogens and their bioactive metabolites play key roles in regulating diverse processes in health and disease. In particular, estrogens and estrogenic metabolites have shown both protective and non-protective effects on disease pathobiology, implicating the importance of this steroid pathway in disease diagnostics and monitoring. All estrogens circulate in a wide range of concentrations, which in some patient cohorts can be extremely low. However, elevated levels of estradiol are reported in disease. For example, in pulmonary arterial hypertension (PAH) elevated levels have been reported in men and postmenopausal women. Conventional immunoassay techniques have come under scrutiny, with their selectivity, accuracy and precision coming into question. Analytical methodologies such as gas and liquid chromatography coupled to single and tandem mass spectrometric approaches (GC–MS, GC–MS/MS, LC–MS and LC–MS/MS) have been developed to quantify endogenous estrogens and in some cases their bioactive metabolites in biological fluids such as urine, serum, plasma and saliva. Liquid-liquid or solid-phase extraction approaches are favoured with derivatization remaining a necessity for detection in lower volumes of sample. The limits of quantitation of individual assays vary but are commonly in the range of 0.5–5 pg/mL for estrone and estradiol, with limits for their bioactive metabolites being higher. This review provides an overview of current approaches for measurement of unconjugated estrogens in biological matrices by MS, highlighting the advances in this field and the challenges remaining for routine use in the clinical and research environment.
KW - bioactive metabolites
KW - estrogen
KW - disease pathobiology
KW - steroid pathway
KW - disease diagnostics
KW - monitoring
UR - https://www.sciencedirect.com/journal/the-journal-of-steroid-biochemistry-and-molecular-biology
U2 - 10.1016/j.jsbmb.2019.04.022
DO - 10.1016/j.jsbmb.2019.04.022
M3 - Article
VL - 192
JO - Journal of Steroid Biochemistry and Molecular Biology
JF - Journal of Steroid Biochemistry and Molecular Biology
SN - 0960-0760
M1 - 105373
ER -