Determination of thyroid hormones in placenta using isotope-dilution liquid chromatography quadrupole time-of-flight mass spectrometry

Zhong-Min Li; Florian Giesert; Daniela Vogt-Weisenhorn; Katharina Maria Main; Niels Erik Skakkebæk; Hannu Kiviranta; Jorma Toppari; Ulla Feldt-Rasmussen; Heqing Shen; Karl-Werner Schramm; Meri De Angelis

doi:10.1016/j.chroma.2017.12.048

Determination of thyroid hormones in placenta using isotope-dilution liquid chromatography quadrupole time-of-flight mass spectrometry

Zhong-Min Li, Florian Giesert, Daniela Vogt-Weisenhorn, Katharina Maria Main, Niels Erik Skakkebæk, Hannu Kiviranta, Jorma Toppari, Ulla Feldt-Rasmussen, Heqing Shen, Karl-Werner Schramm, Meri De Angelis

Department of Clinical Medicine

18 Citations (Scopus)

Abstract

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.

Original language	English
Journal	Journal of Chromatography A
Volume	1534
Pages (from-to)	85-92
ISSN	0021-9673
DOIs	https://doi.org/10.1016/j.chroma.2017.12.048
Publication status	Published - 26 Jan 2018

Keywords

Animals
Chromatography, Liquid
Diiodothyronines
Female
Humans
Isotope Labeling
Isotopes/analysis
Limit of Detection
Liquid-Liquid Extraction
Mass Spectrometry
Mice
Placenta/chemistry
Pregnancy
Reference Standards
Solid Phase Extraction
Thyroid Hormones/analysis
Thyroxine/analysis
Triiodothyronine

Access to Document

10.1016/j.chroma.2017.12.048

Cite this

Li, Z.-M., Giesert, F., Vogt-Weisenhorn, D., Main, K. M., Skakkebæk, N. E., Kiviranta, H., Toppari, J., Feldt-Rasmussen, U., Shen, H., Schramm, K.-W., & De Angelis, M. (2018). Determination of thyroid hormones in placenta using isotope-dilution liquid chromatography quadrupole time-of-flight mass spectrometry. Journal of Chromatography A, 1534, 85-92. https://doi.org/10.1016/j.chroma.2017.12.048

Li, Z-M, Giesert, F, Vogt-Weisenhorn, D, Main, KM , Skakkebæk, NE, Kiviranta, H, Toppari, J, Feldt-Rasmussen, U, Shen, H, Schramm, K-W & De Angelis, M 2018, 'Determination of thyroid hormones in placenta using isotope-dilution liquid chromatography quadrupole time-of-flight mass spectrometry', Journal of Chromatography A, vol. 1534, pp. 85-92. https://doi.org/10.1016/j.chroma.2017.12.048

@article{0cc1d020fe93457fb4552290d37596a8,

title = "Determination of thyroid hormones in placenta using isotope-dilution liquid chromatography quadrupole time-of-flight mass spectrometry",

abstract = "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.",

keywords = "Animals, Chromatography, Liquid, Diiodothyronines, Female, Humans, Isotope Labeling, Isotopes/analysis, Limit of Detection, Liquid-Liquid Extraction, Mass Spectrometry, Mice, Placenta/chemistry, Pregnancy, Reference Standards, Solid Phase Extraction, Thyroid Hormones/analysis, Thyroxine/analysis, Triiodothyronine",

author = "Zhong-Min Li and Florian Giesert and Daniela Vogt-Weisenhorn and Main, {Katharina Maria} and Skakkeb{\ae}k, {Niels Erik} and Hannu Kiviranta and Jorma Toppari and Ulla Feldt-Rasmussen and Heqing Shen and Karl-Werner Schramm and {De Angelis}, Meri",

year = "2018",

month = jan,

day = "26",

doi = "10.1016/j.chroma.2017.12.048",

language = "English",

volume = "1534",

pages = "85--92",

journal = "Journal of Chromatography A",

issn = "0021-9673",

publisher = "Elsevier",

}

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

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 -

Determination of thyroid hormones in placenta using isotope-dilution liquid chromatography quadrupole time-of-flight mass spectrometry

Abstract

Keywords

Access to Document

Fingerprint

Cite this