Paper Sensor Challenges HPLC in Melatonin Testing

Often called the "sleep hormone," melatonin plays a key role in keeping our internal body clock on track, the roughly 24-hour cycle that controls when we feel awake or sleepy, along with a range of physical and mental changes tied to that rhythm. Over the past few decades, melatonin supplements have become a go-to option for people dealing with sleep troubles like insomnia, and their popularity keeps growing.

Unfortunately, there is a catch: Because these products are sold as dietary supplements rather than regulated medications, they do not have to meet the same strict quality standards, which has led to some problems. Research has already documented cases where melatonin products contained far more of the hormone than the label claimed, or were even contaminated with other hormones altogether, sometimes with serious side effects for the people taking them.

Despite these risks, there still was no easy, cheap way to check how much melatonin is in a product. To fix that, a team of Brazilian researchers built a simple paper-based sensor, about the size of a small strip, that can detect melatonin levels in supplements, offering a handy new tool for checking product quality.

To see how well it worked, the team tested their sensor against the industry gold standard, high-performance liquid chromatography (HPLC), using both pill and liquid supplement samples. The results were promising: the paper sensor's readings were off by only about 8% for solid samples and 12% for liquid ones compared to the lab method, a small margin of error for such a simple device. That suggests this low-cost, easy-to-use sensor could become a practical screening tool to help catch mislabeled or contaminated melatonin supplements before they reach consumers. A paper based on the group’s work was published in the journal ACS Omega.¹

What is Melatonin?

Melatonin is one of the body's most important hormones when it comes to regulating our internal clock. It's the chemical behind that roughly 24-hour cycle that shapes when we feel alert or sleepy, and it influences a whole range of physical, mental, and behavioral patterns in living things along the way.²Melatonin is produced mainly by a small gland in the brain called the pineal gland. Once it's released into the bloodstream, it triggers some of the physical changes we typically associate with getting ready for sleep, like a drop in body temperature and blood pressure.³Because of these effects, melatonin shows real promise as a treatment for sleep problems like insomnia.⁴

Does the Paper Sensor Work Well Enough to Replace HPLC Testing for Checking Melatonin Supplements?

In their paper,¹ the Brazilian researchers introduced a simple paper-based test strip for checking melatonin levels in supplements, using a clever color-changing trick based on a classic chemical reaction. When melatonin is present, the paper shifts from white to blue, and the deeper the blue, the more melatonin is in the sample. The article describes the process as similar to a pregnancy test, but for sleep supplements.

The strip did a solid job measuring melatonin in both pill form (0.22 mg per tablet) and liquid drops (0.20 mg per drop), with results that lined up closely with HPLC, once you factor in the small margin of error. The test also showed a very consistent, predictable relationship between color intensity and melatonin concentration across a wide range of doses, and importantly, it did not get confused by other ingredients commonly found in these supplements, like fillers or binders. It only reacted to the melatonin itself, which is exactly what one would want from a reliable screening tool.¹

“The proposed sensor,” write the authors of the paper,¹ “demonstrates excellent potential as an inexpensive tool for quality control, introducing an innovative approach to the use of paper-based microfluidic devices in this field.”

Read More on Similar Topics
LC-MS/MS Links Vitamin D Levels to Sleep Timing

RPLC-MS Profiling Reveals How Sleep Loss Disrupts Circulating Microbial Metabolites

References

1. Ramos, A. J. A.; Brazaca, L. C.; Rossini, E. L. et al. μPADs for a Safer Night's Sleep: An Alternative for Quality Control of Melatonin Pharmaceutical Formulations. ACS Omega 2026, 11 (33), 49733-49738. DOI: 10.1021/acsomega.6c03837
2. Circadian Rhythms. National Institute of General Medical Sciences website. https://nigms.nih.gov/education/fact-sheets/Pages/Circadian-Rhythms.aspx.
3. Li, J.; Somers, V. K.; Xu, H. et al. Trends in Use of Melatonin Supplements Among US Adults, 1999-2018. JAMA 2022, 327 (5), 483-485. DOI: 10.1001/jama.2021.23652
4. Erland, L. A.; Saxena, P. K. Melatonin Natural Health Products and Supplements: Presence of Serotonin and Significant Variability of Melatonin Content. J Clin Sleep Med. 2017, 13 (2), 275-281. DOI: 10.5664/jcsm.6462