Urinary metabolites and antioxidant products of exogenous melatonin in the mouse

Leopoldo Ceraulo, Kristopher W. Krausz, Jeffrey R. Idle, Dun-Xian Tan, Xiaochao Ma, Frank J. Gonzalez

Risultato della ricerca: Article

45 Citazioni (Scopus)

Abstract

Exogenous melatonin is widely used for sleep disorders and has potential value in neuroprotection, cardioprotection and as an antioxidant. Here, a novel method is described for the determination of melatonin and six metabolites in mouse urine by use of LC-MS/MS and GC-MS. LC-MS/MS is used for the measurement of melatonin, N-1-acetyl-5-methoxykynuramine (AMK), N-1-acetyl-N-2-formyl-5-methoxykynuramine (AFMK) and 6-hydroxymelatonin (6-HMEL), while GC/MS is used for the determination of N-[2-(5-methoxy-2-oxo-2,3-dihydro-1H-indol-3-yl)-ethyl]-acetamide (2-OMEL) and cyclic 3-hydroxymelatonin (3-HMEL) with detection limits on column of 0.02-0.5 pmol, depending on the metabolite. Following oral administration of melatonin to mice, a 0-24 hr urine collection revealed the presence of melatonin (0.2% dose), 6-HMEL (37.1%) and NAS (3.1%) comprising > 90% of the total metabolites; AMK and AFMK were also detected at 0.01% each; 2-OMEL was found at 2.2% of the dose, which is > 100 times more than the AMK/AFMK pathway, and comprises > 5% of the melatonin-related material detected in mouse urine. 3-HMEL was largely found as a sulfate conjugate. These studies establish sensitive assays for determination of six melatonin metabolites in mouse urine and confirm the potential for antioxidant activity of melatonin through the identification in vivo of AMK and AFMK, ring-opened metabolites with a high capacity for scavenging reactive oxygen species.
Lingua originaleEnglish
pagine (da-a)343-349
Numero di pagine7
RivistaJournal of Pineal Research
Volume40
Stato di pubblicazionePublished - 2006

Fingerprint

Melatonin
Antioxidants
Urine
Urine Specimen Collection
Sulfates
Oral Administration
Limit of Detection
Reactive Oxygen Species
N-acetyl-5-methoxy kynurenamine

All Science Journal Classification (ASJC) codes

  • Endocrinology

Cita questo

Ceraulo, L., Krausz, K. W., Idle, J. R., Tan, D-X., Ma, X., & Gonzalez, F. J. (2006). Urinary metabolites and antioxidant products of exogenous melatonin in the mouse. Journal of Pineal Research, 40, 343-349.

Urinary metabolites and antioxidant products of exogenous melatonin in the mouse. / Ceraulo, Leopoldo; Krausz, Kristopher W.; Idle, Jeffrey R.; Tan, Dun-Xian; Ma, Xiaochao; Gonzalez, Frank J.

In: Journal of Pineal Research, Vol. 40, 2006, pag. 343-349.

Risultato della ricerca: Article

Ceraulo, L, Krausz, KW, Idle, JR, Tan, D-X, Ma, X & Gonzalez, FJ 2006, 'Urinary metabolites and antioxidant products of exogenous melatonin in the mouse', Journal of Pineal Research, vol. 40, pagg. 343-349.
Ceraulo, Leopoldo ; Krausz, Kristopher W. ; Idle, Jeffrey R. ; Tan, Dun-Xian ; Ma, Xiaochao ; Gonzalez, Frank J. / Urinary metabolites and antioxidant products of exogenous melatonin in the mouse. In: Journal of Pineal Research. 2006 ; Vol. 40. pagg. 343-349.
@article{c9eacffa6a774fb498aa6723717aa716,
title = "Urinary metabolites and antioxidant products of exogenous melatonin in the mouse",
abstract = "Exogenous melatonin is widely used for sleep disorders and has potential value in neuroprotection, cardioprotection and as an antioxidant. Here, a novel method is described for the determination of melatonin and six metabolites in mouse urine by use of LC-MS/MS and GC-MS. LC-MS/MS is used for the measurement of melatonin, N-1-acetyl-5-methoxykynuramine (AMK), N-1-acetyl-N-2-formyl-5-methoxykynuramine (AFMK) and 6-hydroxymelatonin (6-HMEL), while GC/MS is used for the determination of N-[2-(5-methoxy-2-oxo-2,3-dihydro-1H-indol-3-yl)-ethyl]-acetamide (2-OMEL) and cyclic 3-hydroxymelatonin (3-HMEL) with detection limits on column of 0.02-0.5 pmol, depending on the metabolite. Following oral administration of melatonin to mice, a 0-24 hr urine collection revealed the presence of melatonin (0.2{\%} dose), 6-HMEL (37.1{\%}) and NAS (3.1{\%}) comprising > 90{\%} of the total metabolites; AMK and AFMK were also detected at 0.01{\%} each; 2-OMEL was found at 2.2{\%} of the dose, which is > 100 times more than the AMK/AFMK pathway, and comprises > 5{\%} of the melatonin-related material detected in mouse urine. 3-HMEL was largely found as a sulfate conjugate. These studies establish sensitive assays for determination of six melatonin metabolites in mouse urine and confirm the potential for antioxidant activity of melatonin through the identification in vivo of AMK and AFMK, ring-opened metabolites with a high capacity for scavenging reactive oxygen species.",
author = "Leopoldo Ceraulo and Krausz, {Kristopher W.} and Idle, {Jeffrey R.} and Dun-Xian Tan and Xiaochao Ma and Gonzalez, {Frank J.}",
year = "2006",
language = "English",
volume = "40",
pages = "343--349",
journal = "Journal of Pineal Research",
issn = "0742-3098",
publisher = "Wiley-Blackwell",

}

TY - JOUR

T1 - Urinary metabolites and antioxidant products of exogenous melatonin in the mouse

AU - Ceraulo, Leopoldo

AU - Krausz, Kristopher W.

AU - Idle, Jeffrey R.

AU - Tan, Dun-Xian

AU - Ma, Xiaochao

AU - Gonzalez, Frank J.

PY - 2006

Y1 - 2006

N2 - Exogenous melatonin is widely used for sleep disorders and has potential value in neuroprotection, cardioprotection and as an antioxidant. Here, a novel method is described for the determination of melatonin and six metabolites in mouse urine by use of LC-MS/MS and GC-MS. LC-MS/MS is used for the measurement of melatonin, N-1-acetyl-5-methoxykynuramine (AMK), N-1-acetyl-N-2-formyl-5-methoxykynuramine (AFMK) and 6-hydroxymelatonin (6-HMEL), while GC/MS is used for the determination of N-[2-(5-methoxy-2-oxo-2,3-dihydro-1H-indol-3-yl)-ethyl]-acetamide (2-OMEL) and cyclic 3-hydroxymelatonin (3-HMEL) with detection limits on column of 0.02-0.5 pmol, depending on the metabolite. Following oral administration of melatonin to mice, a 0-24 hr urine collection revealed the presence of melatonin (0.2% dose), 6-HMEL (37.1%) and NAS (3.1%) comprising > 90% of the total metabolites; AMK and AFMK were also detected at 0.01% each; 2-OMEL was found at 2.2% of the dose, which is > 100 times more than the AMK/AFMK pathway, and comprises > 5% of the melatonin-related material detected in mouse urine. 3-HMEL was largely found as a sulfate conjugate. These studies establish sensitive assays for determination of six melatonin metabolites in mouse urine and confirm the potential for antioxidant activity of melatonin through the identification in vivo of AMK and AFMK, ring-opened metabolites with a high capacity for scavenging reactive oxygen species.

AB - Exogenous melatonin is widely used for sleep disorders and has potential value in neuroprotection, cardioprotection and as an antioxidant. Here, a novel method is described for the determination of melatonin and six metabolites in mouse urine by use of LC-MS/MS and GC-MS. LC-MS/MS is used for the measurement of melatonin, N-1-acetyl-5-methoxykynuramine (AMK), N-1-acetyl-N-2-formyl-5-methoxykynuramine (AFMK) and 6-hydroxymelatonin (6-HMEL), while GC/MS is used for the determination of N-[2-(5-methoxy-2-oxo-2,3-dihydro-1H-indol-3-yl)-ethyl]-acetamide (2-OMEL) and cyclic 3-hydroxymelatonin (3-HMEL) with detection limits on column of 0.02-0.5 pmol, depending on the metabolite. Following oral administration of melatonin to mice, a 0-24 hr urine collection revealed the presence of melatonin (0.2% dose), 6-HMEL (37.1%) and NAS (3.1%) comprising > 90% of the total metabolites; AMK and AFMK were also detected at 0.01% each; 2-OMEL was found at 2.2% of the dose, which is > 100 times more than the AMK/AFMK pathway, and comprises > 5% of the melatonin-related material detected in mouse urine. 3-HMEL was largely found as a sulfate conjugate. These studies establish sensitive assays for determination of six melatonin metabolites in mouse urine and confirm the potential for antioxidant activity of melatonin through the identification in vivo of AMK and AFMK, ring-opened metabolites with a high capacity for scavenging reactive oxygen species.

UR - http://hdl.handle.net/10447/34453

M3 - Article

VL - 40

SP - 343

EP - 349

JO - Journal of Pineal Research

JF - Journal of Pineal Research

SN - 0742-3098

ER -