Differentiation of diiodothyronines using electrospray ionization tandem mass spectrometry

Zhang, Yuntao; Conrad, Abigail H.; Thoma, Rudy; Conrad, Gary W.

doi:10.1002/jms.971

Cited by 11 publications

(11 citation statements)

References 22 publications

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“…However, the relative abundance of m/z 507.9 from T3 was lower than that from rT3, and the relative abundance of m/z 381.8 in 3,5-T2 was lower than that from 3,3’-T2. The mass spectrometric characteristics of the two T3 isomers and the two T2 isomers in this study are similar to previous observations [38, 39]. Also interesting to note, when CE values increased from 20 v to 35 v, m/z 478.7, [M+H-CIO 2 ] + , became the second most abundant fragment ion for T3.…”

Section: Resultssupporting

confidence: 90%

“…This phenomenon was also observed in previous studies [38, 39]. From chemical structures of these isomers (Fig.…”

Section: Resultssupporting

confidence: 89%

“…3 A2 to A5, B2 to B5), iodine atoms in outer aromatic rings of rT3 and 3,3’-T2 isomers may favor the formation of [M+H-HIO] + or [M+H-H 3 IN] + ions in positive ion mode, contrasted with T3 and 3,5-T2, which may inhibit the loss of iodine in negative ion mode. The varied patterns of MS/MS fragment ions of both isomer pairs of 3,5-T2 and 3,3´-T2 and rT3 and T3 were used to differentiate T3 from rT3, 3,5-T2 from 3,3′-T2 by direct ESI-/MS/MS without LC separation [38, 39]. However, co-existing fragment ions in MS/MS spectra of T2 and T3 isomers could interfere with the accurate quantification for these isomers.…”

Section: Resultsmentioning

confidence: 99%

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Analysis of thyroid hormones in serum by liquid chromatography-tandem mass spectrometry

Wang

Stapleton

2010

Anal Bioanal Chem

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Thyroid hormones are essential hormones for regulating growth and development in humans and wildlife. Methods to monitor precise and low levels of these hormones in serum and tissues are needed to assess overall health, whether from disease considerations or possibly from environmental contaminant exposures. Common and routine methods typically rely upon radio-immunoassays, which can be expensive, and typically only measure T4 and T3, which can be a limitation in fully evaluating impacts on thyroid regulation. In this study we developed an liquid chromatography-tandem mass spectrometry method for the simultaneous analysis of five thyroid hormones including thyroxine (T4), 3,3′,5-triidothyronine (T3), 3,3′,5′-triiodothyronine (rT3; reverse T3), 3,3′-diiodothyronine (3,3′-T2), and 3,5-diiodothyronine (3,5-T2) in serum samples. The LC/MS-MS parameters were optimized and calibrated over a wide concentration range (1.0 to 500 ng/mL) with on-column detection limits of 1.5-7.0 pg. Using spiked bovine serum samples, mean method recoveries were calculated to be 81.3-111.9 % with RSDs of 1.2-9.6 % at spiking levels ranging from 10 to 100 ng/mL. This method was compared with measurements made by standard RIAs and to measurements made in a serum Standard Reference Material (SRM 1951b). Development of this method expands the capacity to measure thyroid hormones by including a larger suite of thyroid hormones, and has promising applications for measuring catabolism of thyroid hormones in vitro.

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Section: Resultssupporting

confidence: 90%

“…This phenomenon was also observed in previous studies [38, 39]. From chemical structures of these isomers (Fig.…”

Section: Resultssupporting

confidence: 89%

Section: Resultsmentioning

confidence: 99%

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Analysis of thyroid hormones in serum by liquid chromatography-tandem mass spectrometry

Wang

Stapleton

2010

Anal Bioanal Chem

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“…In all product ion spectra obtained by MS/MS analysis a loss of a formyl moiety from the respective quasi‐molecular ion [M+H] + was observed. The formation of [M+H‐HCOOH] + fragment ions is also in line with previously published data 28–33. Thus, this transition was used for the detection of each TH by MS/MS.…”

Section: Resultssupporting

confidence: 86%

Development of a validated liquid chromatography/tandem mass spectrometry method for the distinction of thyronine and thyronamine constitutional isomers and for the identification of new deiodinase substrates

Piehl

Heberer

Balizs

et al. 2008

Rapid Comm Mass Spectrometry

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Thyronines (THs) and thyronamines (TAMs) are two groups of endogenous iodine-containing signaling molecules whose representatives differ from each other only regarding the number and/or the position of the iodine atoms. Both groups of compounds are substrates of three deiodinase isozymes, which catalyze the sequential reductive removal of iodine from the respective precursor molecule. In this study, a novel analytical method applying liquid chromatography/tandem mass spectrometry (LC-MS/MS) was developed. This method permitted the unequivocal, simultaneous identification and quantification of all THs and TAMs in the same biological sample. Furthermore, a liquid-liquid extraction procedure permitting the concurrent isolation of all THs and TAMs from biological matrices, namely deiodinase (Dio) reaction mixtures, was established. Method validation experiments with extracted TH and TAM analytes demonstrated that the method was selective, devoid of matrix effects, sensitive, linear over a wide range of analyte concentrations and robust in terms of reproducible recoveries, process efficiencies as well as intra-assay and inter-assay stability parameters. The method was applied to study the deiodination reactions of iodinated THs catalyzed by the three deiodinase isozymes. With the HPLC protocol developed herein, sufficient chromatographic separation of all constitutional TH and TAM isomers was achieved. Accordingly, the position of each iodine atom removed from a TH substrate in a Dio-catalyzed reaction was backtracked unequivocally. While several established deiodination reactions were verified, two as yet unknown reactions, namely the phenolic ring deiodination of 3',5'-diiodothyronine (3',5'-T2) by Dio2 and the tyrosyl ring deiodination of 3-monoiodothyronine (3-T1) by Dio3, were newly identified.

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“…For this purpose, we used a newly developed immunoassay (20), representing the only currently available method to determine serum 3,5-T2 concentrations in humans (26)(27)(28). Our data revealed significant bell-shaped associations of serum 3,5-T2 concentrations with serum glucose concentration and TSH concentrations in the fasting state, pointing toward a versatile role of circulating 3,5-T2 in human metabolism.…”

Section: Discussionmentioning

confidence: 90%

Translating Pharmacological Findings from Hypothyroid Rodents to Euthyroid Humans: Is There a Functional Role of Endogenous 3,5-T2?

Pietzner

Lehmphul

Friedrich

et al. 2015

Thyroid

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Background: During the last two decades, it has become obvious that 3,5-diiodothyronine (3,5-T2), a wellknown endogenous metabolite of the thyroid hormones thyroxine (T4) or triiodothyronine (T3), not only represents a simple degradation intermediate of the former but also exhibits specific metabolic activities. Administration of 3,5-T2 to hypothyroid rodents rapidly stimulated their basal metabolic rate, prevented highfat diet-induced obesity as well as steatosis, and increased oxidation of long-chain fatty acids. Objective: The aim of the present study was to analyze associations between circulating 3,5-T2 in human serum and different epidemiological parameters, including age, sex, or smoking, as well as measures of anthropometry, glucose, and lipid metabolism. Methods: 3,5-T2 concentrations were measured by a recently developed immunoassay in sera of 761 euthyroid participants of the population-based Study of Health in Pomerania. Subsequently, analysis of variance and multivariate linear regression analysis were performed. Results: Serum 3,5-T2 concentrations exhibited a right-skewed distribution, resulting in a median serum concentration of 0.24 nM (1st quartile: 0.20 nM; 3rd quartile: 0.37 nM). Significant associations between 3,5-T2 and serum fasting glucose, thyrotropin (TSH), as well as leptin concentrations were detected ( p < 0.05). Interestingly, the association to leptin concentrations seemed to be mediated by TSH. Age, sex, smoking, and blood lipid profile parameters did not show significant associations with circulating 3,5-T2. Conclusion: Our findings from a healthy euthyroid population may point toward a physiological link between circulating 3,5-T2 and glucose metabolism.

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Differentiation of diiodothyronines using electrospray ionization tandem mass spectrometry

Cited by 11 publications

References 22 publications

Analysis of thyroid hormones in serum by liquid chromatography-tandem mass spectrometry

Analysis of thyroid hormones in serum by liquid chromatography-tandem mass spectrometry

Development of a validated liquid chromatography/tandem mass spectrometry method for the distinction of thyronine and thyronamine constitutional isomers and for the identification of new deiodinase substrates

Translating Pharmacological Findings from Hypothyroid Rodents to Euthyroid Humans: Is There a Functional Role of Endogenous 3,5-T2?

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