TY - JOUR
T1 - Identification and quantification of 3-iodothyronamine metabolites in mouse serum using liquid chromatography-tandem mass spectrometry
AU - Hackenmueller, Sarah A.
AU - Scanlan, Thomas S.
N1 - Funding Information:
This work was supported by a grant from the NIH ( DK-52798 , T.S.S.). This work used instrumentation maintained by the Bioanalytical Shared Resource/Pharmacokinetics Core at Oregon Health & Science University. We are grateful to Warren Wood, Aaron Nilsen and Federico Espinosa for preparing synthetic standards.
PY - 2012/9/21
Y1 - 2012/9/21
N2 - 3-Iodothyronamine (T1AM) is an endogenous derivative of thyroxine. Recently there have been numerous reports of analytical methods to quantify endogenous T1AM levels, but substantial discrepancies in concentration depending on the method of analysis (LC-MS/MS or immunoassay) suggest endogenous T1AM may be covalently modified in vivo. Using information dependent acquisition methods to perform unbiased scans for T1AM metabolites following a single IP injection in mice, we have identified O-sulfonate-T1AM, N-acetyl-T1AM and T1AM-glucuronide as conjugates occurring in vivo, as well as the oxidatively deaminated 3-iodothyroacetic acid and non-iodinated thyroacetic acid. 3-iodothyroacetic acid, O-sulfonate-T1AM and T1AM-glucuronide are present in serum at greater concentrations that unmodified T1AM and all metabolites are extensively distributed to tissues. These results suggest covalent modifications of T1AM may play a critical role in regulating distribution and biological activity of T1AM, and analytical methods to quantify endogenous T1AM should be able to account for these metabolites as well.
AB - 3-Iodothyronamine (T1AM) is an endogenous derivative of thyroxine. Recently there have been numerous reports of analytical methods to quantify endogenous T1AM levels, but substantial discrepancies in concentration depending on the method of analysis (LC-MS/MS or immunoassay) suggest endogenous T1AM may be covalently modified in vivo. Using information dependent acquisition methods to perform unbiased scans for T1AM metabolites following a single IP injection in mice, we have identified O-sulfonate-T1AM, N-acetyl-T1AM and T1AM-glucuronide as conjugates occurring in vivo, as well as the oxidatively deaminated 3-iodothyroacetic acid and non-iodinated thyroacetic acid. 3-iodothyroacetic acid, O-sulfonate-T1AM and T1AM-glucuronide are present in serum at greater concentrations that unmodified T1AM and all metabolites are extensively distributed to tissues. These results suggest covalent modifications of T1AM may play a critical role in regulating distribution and biological activity of T1AM, and analytical methods to quantify endogenous T1AM should be able to account for these metabolites as well.
KW - 3-Iodothyronamine
KW - Information dependent acquisition
KW - LC-MS/MS
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U2 - 10.1016/j.chroma.2012.07.052
DO - 10.1016/j.chroma.2012.07.052
M3 - Article
C2 - 22885046
AN - SCOPUS:84865391086
SN - 0021-9673
VL - 1256
SP - 89
EP - 97
JO - Journal of Chromatography A
JF - Journal of Chromatography A
ER -