Quantitation of melatonin and n-acetylserotonin in human plasma by nanoflow LC-MS/MS and electrospray LC-MS/MS

Melatonin (MEL) and its chemical precursor N‐acetylserotonin (NAS) are believed to be potential biomarkers for sleep‐related disorders. Measurement of these compounds, however, has proven to be difficult due to their low circulating levels, especially that of NAS. Few methods offer the sensitivity,...

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Bibliographic Details
Published in:Journal of mass spectrometry. Vol. 47; no. 3; pp. 277 - 285
Main Authors: Carter, Melissa D., Wade Calcutt, M., Malow, Beth A., Rose, Kristie L., Hachey, David L.
Format: Journal Article
Language:English
Published: Chichester, UK John Wiley & Sons, Ltd 01.03.2012
Wiley
Subjects:
Adult
Analysis
autism spectrum disorder
Biological and medical sciences
Child
Child clinical studies
Child, Preschool
Chromatography, Liquid - methods
Developmental disorders
Female
General pharmacology
Humans
Infantile autism
Investigative techniques, diagnostic techniques (general aspects)
Male
Medical sciences
Melatonin
Melatonin - blood
Melatonin - pharmacokinetics
Miscellaneous. Technology
N-acetylserotonin
Nanoflow LC-MS/MS
Nanotechnology
Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques
Pharmacology. Drug treatments
Psychology. Psychoanalysis. Psychiatry
Psychopathology. Psychiatry
Reproducibility of Results
Serotonin - analogs & derivatives
Serotonin - blood
Serotonin - pharmacokinetics
Spectrometry, Mass, Electrospray Ionization - methods
Tandem Mass Spectrometry - methods
Biological fluid
Tandem mass spectrometry
Melatonin
Chemical analysis
Aminoacid derivative hormone
HPLC chromatography
Tryptamine derivatives
N-acetylserotonin
Developmental disorder
Electrospray
Blood
Blood plasma
Clinical biology
Biosynthesis precursor
autism spectrum disorder
Child
Quantitative analysis
Human
Healthy subject
Coupled method
Oral administration
Patient
Endogenous substance
Autism
Nanoflow LC-MS/MS
Indole derivatives
Pharmacokinetics
ISSN:1076-5174, 1096-9888, 1096-9888
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Summary:Melatonin (MEL) and its chemical precursor N‐acetylserotonin (NAS) are believed to be potential biomarkers for sleep‐related disorders. Measurement of these compounds, however, has proven to be difficult due to their low circulating levels, especially that of NAS. Few methods offer the sensitivity, specificity and dynamic range needed to monitor MEL and its precursors and metabolites in small blood samples, such as those obtained from pediatric patients. In support of our ongoing study to determine the safety, tolerability and PK dosing strategies for MEL in treating insomnia in children with autism spectrum disorder, two highly sensitive LC‐MS/MS assays were developed for the quantitation of MEL and precursor NAS at pg/mL levels in small volumes of human plasma. A validated electrospray ionization (ESI) method was used to quantitate high levels of MEL in PK studies, and a validated nanospray (nESI) method was developed for quantitation of MEL and NAS at endogenous levels. In both assays, plasma samples were processed by centrifugal membrane dialysis after addition of stable isotopic internal standards, and the components were separated by either conventional LC using a Waters SymmetryShield RP18 column (2.1 × 100 mm, 3.5 µm) or on a polyimide‐coated, fused‐silica capillary self‐packed with 17 cm AquaC18 (3 µm, 125 Å). Quantitation was done using the SRM transitions m/z 233 → 174 and m/z 219 → 160 for MEL and NAS, respectively. The analytical response ratio versus concentration curves were linear for MEL (nanoflow LC: 11.7–1165 pg/mL, LC: 1165–116500 pg/mL) and for NAS (nanoflow LC: 11.0–1095 pg/mL). Copyright © 2012 John Wiley & Sons, Ltd.
Bibliography:ArticleID:JMS2051
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content type line 23
ISSN:1076-5174
1096-9888
1096-9888
DOI:10.1002/jms.2051