Measurement of plasma melatonin is important in studies of sleep disorders and neurodegenerative diseases and is also increasingly associated with cardiometabolic diseases and cancer. There is currently an increase in the usage of melatonin in the population. However, commercially available and reliable melatonin assays are lacking. Here we present a rapid and simple LC-MS/MS-based method for plasma melatonin in a clinical laboratory. The method demonstrates a limit of detection of 5 ng/L and inter-assay imprecision p p < 0.03) but demonstrated a substantial bias. We conclude that our simple LC-MS/MS method can detect biologically relevant changes in plasma melatonin and may enable insight into circadian biology in humans. We propose that the observed differences between melatonin assays could be clarified by the distribution of reference plasma melatonin material and that additional studies are needed to fully understand the minimum circulating levels of melatonin in the daytime.
Albrethsen et al. (2026) studied this question.