title: Measurement of melatonin in body fluids: standards, protocols and procedures.
abstract: OBJECTIVE
  The circadian rhythm of melatonin in saliva or plasma, or of the melatonin metabolite 6-sulfatoxymelatonin (a6MTs) in urine, is a defining feature of suprachiasmatic nucleus (SCN) function, the body's endogenous oscillatory pacemaker. The primary objective of this review is to ascertain the clinical benefits and limitations of current methodologies employed for detection and quantification of melatonin in biological fluids and tissues.
  
  
  METHODS
  A search of the English-language literature (Medline) and a systematic review of published articles were carried out.
  
  
  METHODS
  Articles that specified both the methodology for quantifying melatonin and indicated the clinical purpose were chosen for inclusion in the review.
  
  
  METHODS
  The authors critically evaluated the methodological issues associated with various tools and techniques (e.g. standards, protocols, and procedures).
  
  
  RESULTS
  Melatonin measurements are useful for evaluating problems related to the onset or offset of sleep and for assessing phase delays or advances of rhythms in entrained individuals. They have also become an important tool for psychiatric diagnosis, their use being recommended for phase typing in patients suffering from sleep and mood disorders. Additionally, there has been a continuous interest in the use of melatonin as a marker for neoplasms of the pineal region. Melatonin decreases such as found with aging are or post pinealectomy can cause alterations in the sleep/wake cycle. The development of sensitive and selective methods for the precise detection of melatonin in tissues and fluids has increasingly been shown to have direct relevance for clinical decision making.
  
  
  CONCLUSIONS
  Due to melatonin's low concentration, as well as the coexistence of numerous other compounds in the blood, the routine determination of melatonin has been an analytical challenge. The available evidence indicates however that these challenges can be overcome and consequently that evaluation of melatonin's presence and activity can be an accessible and useful tool for clinical diagnosis.
authors.affiliation: Departamento de Química e Ciências Ambientais, IBILCE, UNESP, Rua Cristóvão Colombo 2265, CEP 15054-000, São José do Rio Preto, SP, Brazil.
authors.forename: Eduardo Alves
authors.initials: EA
authors.lastname: de Almeida
authors.forename: Paolo
authors.initials: P
authors.lastname: Di Mascio
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Harumi
authors.forename: D Warren
authors.initials: DW
authors.lastname: Spence
authors.forename: Adam
authors.initials: A
authors.lastname: Moscovitch
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Hardeland
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Cardinali
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Brown
authors.forename: S R
authors.initials: SR
authors.lastname: Pandi-Perumal
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D001826:Body Fluids / Q000737:chemistry* / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid / Q000379:methods / Q000592:standards; D002940:Circadian Rhythm / Q000502:physiology; D019075:Electrophoresis, Capillary / Q000379:methods / Q000592:standards; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods / Q000592:standards; D006801:Humans; D008550:Melatonin / Q000031:analogs & derivatives / Q000032:analysis* / Q000097:blood / Q000378:metabolism; D012463:Saliva / Q000737:chemistry / Q000378:metabolism; D000078202:Systematic Reviews as Topic
chemical_list: D015415:Biomarkers; C054513:6-sulfatoxymelatonin; D008550:Melatonin