TY - JOUR
T1 - Determination of thyroid hormones in placenta using isotope-dilution liquid chromatography quadrupole time-of-flight mass spectrometry
AU - Li, Zhong-Min
AU - Giesert, Florian
AU - Vogt-Weisenhorn, Daniela
AU - Main, Katharina Maria
AU - Skakkebæk, Niels Erik
AU - Kiviranta, Hannu
AU - Toppari, Jorma
AU - Feldt-Rasmussen, Ulla
AU - Shen, Heqing
AU - Schramm, Karl-Werner
AU - De Angelis, Meri
N1 - Copyright © 2017 Elsevier B.V. All rights reserved.
PY - 2018/1/26
Y1 - 2018/1/26
N2 - The transplacental passage of thyroid hormones (THs) is of great significance since the maternal THs are vitally important in ensuring the normal fetal development. In this paper, we determined the concentrations of seven THs, viz. L-thyroxine (T4), 3,3′,5-triiodo-L-thyronine (T3), 3,3′,5′-triiodo-L-thyronine (rT3), 3,3′-diiodo-L-thyronine (T2), 3,5-diiodo-L-thyronine (rT2), 3-iodo-L-thyronine (T1) and 3-iodothyronamine (T1AM), in placenta using isotope dilution liquid chromatography quadrupole time-of-flight mass spectrometry. We optimized the method using isotopically labeled quantification standards (13C6-T4, 13C6-T3, 13C6-rT3 and 13C6-T2) and recovery standard (13C12-T4) in combination with solid-liquid extraction, liquid–liquid extraction and solid phase extraction. The linearity was obtained in the range of 0.5–150 pg uL−1 with R2 values >0.99. The method detection limits (MDLs) ranged from 0.01 ng g−1 to 0.2 ng g−1, while the method quantification limits (MQLs) were between 0.04 ng g−1 and 0.7 ng g−1. The spike-recoveries for THs (except for T1 and T1AM) were in the range of 81.0%–112%, with a coefficient of variation (CV) of 0.5–6.2%. The intra-day CVs and inter-day CVs were 0.5%–10.3% and 1.19%–8.88%, respectively. Concentrations of the THs were 22.9–35.0 ng g−1 T4, 0.32–0.46 ng g−1 T3, 2.86–3.69 ng g−1 rT3, 0.16–0.26 ng g−1 T2, and < MDL for other THs in five human placentas, and 2.05–3.51 ng g−1 T4, 0.37–0.62 ng g−1 T3, 0.96–1.3 ng g−1 rT3, 0.07–0.13 ng g−1 T2 and < MDL for other THs in five mouse placentas. The presence of T2 was tracked in placenta for the first time. This method with improved selectivity and sensitivity allows comprehensive evaluation of TH homeostasis in research of metabolism and effects of environmental contaminant exposures.
AB - The transplacental passage of thyroid hormones (THs) is of great significance since the maternal THs are vitally important in ensuring the normal fetal development. In this paper, we determined the concentrations of seven THs, viz. L-thyroxine (T4), 3,3′,5-triiodo-L-thyronine (T3), 3,3′,5′-triiodo-L-thyronine (rT3), 3,3′-diiodo-L-thyronine (T2), 3,5-diiodo-L-thyronine (rT2), 3-iodo-L-thyronine (T1) and 3-iodothyronamine (T1AM), in placenta using isotope dilution liquid chromatography quadrupole time-of-flight mass spectrometry. We optimized the method using isotopically labeled quantification standards (13C6-T4, 13C6-T3, 13C6-rT3 and 13C6-T2) and recovery standard (13C12-T4) in combination with solid-liquid extraction, liquid–liquid extraction and solid phase extraction. The linearity was obtained in the range of 0.5–150 pg uL−1 with R2 values >0.99. The method detection limits (MDLs) ranged from 0.01 ng g−1 to 0.2 ng g−1, while the method quantification limits (MQLs) were between 0.04 ng g−1 and 0.7 ng g−1. The spike-recoveries for THs (except for T1 and T1AM) were in the range of 81.0%–112%, with a coefficient of variation (CV) of 0.5–6.2%. The intra-day CVs and inter-day CVs were 0.5%–10.3% and 1.19%–8.88%, respectively. Concentrations of the THs were 22.9–35.0 ng g−1 T4, 0.32–0.46 ng g−1 T3, 2.86–3.69 ng g−1 rT3, 0.16–0.26 ng g−1 T2, and < MDL for other THs in five human placentas, and 2.05–3.51 ng g−1 T4, 0.37–0.62 ng g−1 T3, 0.96–1.3 ng g−1 rT3, 0.07–0.13 ng g−1 T2 and < MDL for other THs in five mouse placentas. The presence of T2 was tracked in placenta for the first time. This method with improved selectivity and sensitivity allows comprehensive evaluation of TH homeostasis in research of metabolism and effects of environmental contaminant exposures.
KW - Animals
KW - Chromatography, Liquid
KW - Diiodothyronines
KW - Female
KW - Humans
KW - Isotope Labeling
KW - Isotopes/analysis
KW - Limit of Detection
KW - Liquid-Liquid Extraction
KW - Mass Spectrometry
KW - Mice
KW - Placenta/chemistry
KW - Pregnancy
KW - Reference Standards
KW - Solid Phase Extraction
KW - Thyroid Hormones/analysis
KW - Thyroxine/analysis
KW - Triiodothyronine
U2 - 10.1016/j.chroma.2017.12.048
DO - 10.1016/j.chroma.2017.12.048
M3 - Journal article
C2 - 29307529
SN - 0021-9673
VL - 1534
SP - 85
EP - 92
JO - Journal of Chromatography A
JF - Journal of Chromatography A
ER -