Measurement of melatonin in body fluids: Standards, protocols and procedures

Abstract

Background and PurposeThe 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.Data IdentificationA search of the English-language literature (Medline) and a systematic review of published articles were carried out.Study SelectionArticles that specified both the methodology for quantifying melatonin and indicated the clinical purpose were chosen for inclusion in the review.Data ExtractionThe authors critically evaluated the methodological issues associated with various tools and techniques (e.g. standards, protocols, and procedures).Results of Data SynthesisMelatonin 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.ConclusionsDue 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.

Artificial light-at-night – a novel lifestyle risk factor for metabolic disorder and cancer morbidity

“…In premenopausal and postmenopausal women, urinary 6-sulfatoxymelatonin (6-SMT) levels, the major urinary metabolite of MLT [194], show an inverse relation with risk of breast cancer [195,196]. Additionally, the inverse relationship between 6-SMT and breast cancer risk has been confirmed by other case-control studies in women [197].…”

“…MLT levels can be directly determined virtually in all body fluids, including blood, saliva, and urine, using straightforward non-invasive methods. The most pervasive protocols for determination of MLT in blood, urine, and saliva are radioimmunoassay and enzyme-linked immunoassay [194]. The major MLT metabolite in urine, 6-SMT, reliable reflects pineal MLT secretion in human and the metabolite circadian rhythm can faithfully constitute a clinical diagnosis of circadian disruption-related disorders [226].…”

Development of a Fully-automated On-line Oxidation Column-switching HPLC System for the Determination of Endogenous Melatonin in Human Clinical Samples

“…However, the amount of endogenous melatonin is extremely low, and a 1 -5 mL blood sample is needed for the determination of melatonin by the methods already reported. [17][18][19][20][21][22][23][24][25][26][27] To obtain 1 -5 mL of blood, blood sampling from the cubital vein is normally required, and it is practically a severe task for patients to measure the circadian rhythm of melatonin (blood should be obtained 6 -8 times within one day). Therefore, a highly sensitive and selective analytical method, which can determine endogenous melatonin using 10 -100 μL of plasma (100 μL of plasma can be obtained by a less invasive method) is required.…”

Diurnal and seasonal changes in endogenous melatonin levels in the blood plasma in dogs

“…In the literature there is a number of works describing both diurnal and seasonal changes in MLT levels in the blood plasma of animals (Andersson 2001, Diekman et al 2002. The most common methods for determination of melatonin in blood are radio-immunoassay (RIA) and enzymelinked immune-sorbent assay (ELISA) (Middleton 2006, De Almeida et al 2011. In this study, we deCorrespondence to: R.S.…”