{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T23:18:28Z","timestamp":1788218308902,"version":"build-2803163510"},"reference-count":21,"publisher":"American Chemical Society (ACS)","issue":"33","license":[{"start":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T00:00:00Z","timestamp":1786665600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001807","name":"Funda??o de Amparo ? i Pesquisa do Estado de S?o Paulo","doi-asserted-by":"publisher","award":["2018\/19750-3"],"award-info":[{"award-number":["2018\/19750-3"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda??o de Amparo ? i Pesquisa do Estado de S?o Paulo","doi-asserted-by":"publisher","award":["2019\/19235-4"],"award-info":[{"award-number":["2019\/19235-4"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda??o de Amparo ? i Pesquisa do Estado de S?o Paulo","doi-asserted-by":"publisher","award":["2022\/05366-2"],"award-info":[{"award-number":["2022\/05366-2"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda??o de Amparo ? i Pesquisa do Estado de S?o Paulo","doi-asserted-by":"publisher","award":["2023\/10141-2"],"award-info":[{"award-number":["2023\/10141-2"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda??o de Amparo ? i Pesquisa do Estado de S?o Paulo","doi-asserted-by":"publisher","award":["2025\/26623-1"],"award-info":[{"award-number":["2025\/26623-1"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002322","name":"Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior","doi-asserted-by":"publisher","award":["001"],"award-info":[{"award-number":["001"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico","doi-asserted-by":"publisher","award":["139116\/2021-4"],"award-info":[{"award-number":["139116\/2021-4"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico","doi-asserted-by":"publisher","award":["308835\/2019-0"],"award-info":[{"award-number":["308835\/2019-0"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico","doi-asserted-by":"publisher","award":["408338\/2024-5"],"award-info":[{"award-number":["408338\/2024-5"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,25]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Melatonin, known as the \u201csleep hormone,\u201d has its primary function in regulating the circadian cycle, a 24 h sleep\u2013wake pattern that leads to significant physical, mental, and behavioral changes. The use of melatonin in pharmaceutical formulations gained popularity as a tool to combat sleep disorders such as insomnia and has been increasing in the last few decades. Melatonin-based pharmaceutical formulations are classified as dietary supplements, which leads to a different perspective on the necessity of strict quality control for these products. There are already extensive descriptions in the literature of the serious side effects associated with the administration of those formulations, including, for example, higher dosages than indicated on the label or contamination by other hormones. Still, there is a gap in devices that could make an easy and low-cost determination of melatonin. This work presents a paper-based sensor for the quality control of melatonin in pharmaceutical formulations, utilizing the modified Van Urk reaction. This reaction causes a color change from white to blue on the paper surface, correlating with the melatonin concentration. The constructed sensor performed well in quantifying melatonin in solid (0.22 mg\/tablet) and liquid (0.20 mg\/drop) pharmaceutical formulations, considering the maximum standard deviation when compared with results obtained by a gold-standard technique (liquid chromatography). The developed method demonstrated good linearity (R2 = 0.9915) over a melatonin concentration range of 40\u2013300 mg L\u20131 and exhibited a specific response to the hormone when tested against the vehicles and excipients of the pharmaceutical formulations. Therefore, the proposed sensor 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.<\/jats:p>","DOI":"10.1021\/acsomega.6c03837","type":"journal-article","created":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T12:02:13Z","timestamp":1786708933000},"page":"49733-49738","source":"Crossref","is-referenced-by-count":0,"title":["\u03bcPADs for a Safer Night\u2019s Sleep: An Alternative\nfor Quality Control of Melatonin Pharmaceutical Formulations"],"prefix":"10.1021","volume":"11","author":[{"given":"Ana Julia Aparecida","family":"Ramos","sequence":"first","affiliation":[{"name":"Universidade de Sa\u0303o Paulo , , , ,","place":["Sa\u0303o Carlos, SP, Brazil, 13566-590"]},{"name":"Instituto Nacional de Cie\u0302ncia e Tecnologia de Bioanali\u0301tica \u2212 Lauro Kubota (INCTBio-LK) , , ,","place":["Campinas, SP, Brazil, 13083-970"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0456-7552","authenticated-orcid":true,"given":"Lai\u0301s Canniatti","family":"Brazaca","sequence":"additional","affiliation":[{"name":"Universidade de Sa\u0303o Paulo , , , ,","place":["Sa\u0303o Carlos, SP, Brazil, 13566-590"]},{"name":"Instituto Nacional de Cie\u0302ncia e Tecnologia de Bioanali\u0301tica \u2212 Lauro Kubota (INCTBio-LK) , , ,","place":["Campinas, SP, Brazil, 13083-970"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduardo Luiz","family":"Rossini","sequence":"additional","affiliation":[{"name":"Universidade de Sa\u0303o Paulo , , , ,","place":["Sa\u0303o Carlos, SP, Brazil, 13566-590"]},{"name":"Instituto Nacional de Cie\u0302ncia e Tecnologia de Bioanali\u0301tica \u2212 Lauro Kubota (INCTBio-LK) , , ,","place":["Campinas, SP, Brazil, 13083-970"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manoel de Jesus de Aquino","family":"Lima","sequence":"additional","affiliation":[{"name":"Universidade de Sa\u0303o Paulo , , , ,","place":["Sa\u0303o Carlos, SP, Brazil, 13566-590"]},{"name":"Instituto Nacional de Cie\u0302ncia e Tecnologia de Bioanali\u0301tica \u2212 Lauro Kubota (INCTBio-LK) , , ,","place":["Campinas, SP, Brazil, 13083-970"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7351-8220","authenticated-orcid":true,"given":"Emanuel","family":"Carrilho","sequence":"additional","affiliation":[{"name":"Universidade de Sa\u0303o Paulo , , , ,","place":["Sa\u0303o Carlos, SP, Brazil, 13566-590"]},{"name":"Instituto Nacional de Cie\u0302ncia e Tecnologia de Bioanali\u0301tica \u2212 Lauro Kubota (INCTBio-LK) , , ,","place":["Campinas, SP, Brazil, 13083-970"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,8,14]]},"reference":[{"key":"2026083119115851900_cit1","unstructured":"National Institute of General Medical Sciences.\n          .  Circadian Rhythms. National Institute of General Medical Sciences. https:\/\/nigms.nih.gov\/education\/fact-sheets\/Pages\/Circadian-Rhythms.aspx."},{"issue":"5","key":"2026083119115851900_cit2","doi-asserted-by":"publisher","first-page":"483","DOI":"10.1001\/jama.2021.23652","article-title":"Trends in Use of Melatonin Supplements\namong US Adults,\n1999\u20132018","volume":"327","author":"Li","year":"2022","journal-title":"JAMA"},{"issue":"02","key":"2026083119115851900_cit3","doi-asserted-by":"publisher","first-page":"275","DOI":"10.5664\/jcsm.6462","article-title":"Melatonin Natural\nHealth Products and Supplements:\nPresence of Serotonin and Significant Variability of Melatonin Content","volume":"13","author":"Erland","year":"2017","journal-title":"Journal of Clinical Sleep Medicine"},{"issue":"02","key":"2026083119115851900_cit4","doi-asserted-by":"publisher","first-page":"163","DOI":"10.5664\/jcsm.6434","article-title":"Poor Quality\nControl of Over-The-Counter Melatonin:\nWhat They Say Is Often Not What You Get","volume":"13","author":"Grigg-Damberger","year":"2017","journal-title":"Journal\nof Clinical Sleep Medicine"},{"issue":"1","key":"2026083119115851900_cit5","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1080\/00387019808006771","article-title":"Colorimetric,\nand Spectrofluorimetric\nMethods for the Determination of Melatonin in Tablets and Serum","volume":"31","author":"Gazy","year":"1998","journal-title":"Spectrosc. Lett."},{"issue":"5","key":"2026083119115851900_cit6","doi-asserted-by":"publisher","first-page":"1824","DOI":"10.1073\/pnas.91.5.1824","article-title":"Effect\nof Inducing Nocturnal Serum Melatonin Concentrations in Daytime on\nSleep, Mood, Body Temperature, and Performance","volume":"91","author":"Dollins","year":"1994","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"2026083119115851900_cit7","unstructured":"Jose\u0301 Hulle Pereira, B.\n          \n          Melatonina:\npara que serve? - Artigo.  NeuroDrops. https:\/\/neurodrops.com.br\/artigos\/medicina-do-sono\/melatonina-para-que-serve-21 (accessed 2023-08-26)."},{"issue":"2","key":"2026083119115851900_cit8","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1385\/ENDO:27:2:189","article-title":"A Review of the\nMultiple Actions of Melatonin on the Immune System","volume":"27","author":"Carrillo-Vico","year":"2005","journal-title":"Endocrine"},{"issue":"4","key":"2026083119115851900_cit9","doi-asserted-by":"publisher","first-page":"8638","DOI":"10.3390\/ijms14048638","article-title":"Melatonin: Buffering\nthe Immune System","volume":"14","author":"Carrillo-Vico","year":"2013","journal-title":"International Journal of\nMolecular Sciences"},{"issue":"7","key":"2026083119115851900_cit10","doi-asserted-by":"publisher","first-page":"14575","DOI":"10.3390\/ijms140714575","article-title":"Melatonin in Alzheimer\u2019s Disease","volume":"14","author":"Lin","year":"2013","journal-title":"International\nJournal of Molecular Sciences"},{"key":"2026083119115851900_cit11","article-title":"Doctors concerned melatonin\nis not fully regulated\nby FDA","volume-title":"Sermo","author":"Sermo Team.","year":"2023"},{"key":"2026083119115851900_cit12","unstructured":"Granchi, G.\n          \n          Anvisa aprova suplementos\nde melatonina, mas substa\u0302ncia na\u0303o traz benefi\u0301cios. https:\/\/www.uol.com.br\/vivabem\/noticias\/redacao\/2021\/11\/03\/anvisa-aprova-melatonina-para-suplementos-substancia-traz-beneficios.htm (accessed 2023-08-26)."},{"issue":"6","key":"2026083119115851900_cit13","doi-asserted-by":"publisher","first-page":"431","DOI":"10.1002\/(SICI)1099-0801(199910)13:6&lt;431::AID-BMC906&gt;3.0.CO;2-O","article-title":"Determination of melatonin\nin pharmaceutical formulations and human plasma by gas chromatography-electron\nimpact mass spectrometry","volume":"13","author":"Covaci","year":"1999","journal-title":"Biomed Chromatogr."},{"key":"2026083119115851900_cit14","unstructured":"Ministe\u0301rio da Sau\u0301de - MS Age\u0302ncia\nNacional de\nVigila\u0302ncia Sanita\u0301ria -ANVISA. [s.l: s.n.]. Disponi\u0301vel\nem: https:\/\/antigo.anvisa.gov.br\/documents\/10181\/6485886\/RDC_843_2024_.pdf\/6018cc13-f7ea-4a24-9bb4-be7e708fb5e8#:~:text=Fica%20estabelecido%20o%20prazo%20at%C3%A9."},{"key":"2026083119115851900_cit15","doi-asserted-by":"publisher","first-page":"64","DOI":"10.3389\/fpls.2017.00064","article-title":"A Simple, Rapid Method for Determination\nof Melatonin\nin Plant Tissues by UPLC Coupled with High-Resolution Orbitrap Mass\nSpectrometry","volume":"8","author":"Ye","year":"2017","journal-title":"Frontiers in Plant Science"},{"issue":"2021","key":"2026083119115851900_cit16","doi-asserted-by":"publisher","first-page":"119285","DOI":"10.1016\/j.saa.2020.119285","article-title":"Paper Microfluidic\nDevice Using Carbon Dots to Detect Glucose and Lactate in Saliva Samples","volume":"248","author":"Rossini","year":"2021","journal-title":"Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy"},{"issue":"1","key":"2026083119115851900_cit17","doi-asserted-by":"publisher","first-page":"12335","DOI":"10.1038\/s41598-017-12549-3","article-title":"A Printed\nMulticomponent Paper Sensor\nfor Bacterial Detection","volume":"7","author":"Ali","year":"2017","journal-title":"Sci. Rep."},{"issue":"2","key":"2026083119115851900_cit18","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1016\/S0021-9673(00)89300-0","article-title":"The van Urk-Salkowski\nreagent\u2500A sensitive and specific chromogenic reagent for silica\ngel thin-layer chromatographic detection and identification of indole\nderivatives","volume":"132","author":"Ehmann","year":"1977","journal-title":"J. Chromatogr."},{"issue":"6","key":"2026083119115851900_cit19","doi-asserted-by":"publisher","first-page":"1174","DOI":"10.1080\/10408398.2014.967834","article-title":"Food Adulteration:\nSources, Health Risks, and Detection Methods","volume":"57","author":"Bansal","year":"2017","journal-title":"Critical Reviews in Food Science and Nutrition"},{"key":"2026083119115851900_cit20","volume-title":"Guidelines for Single\nLaboratory Validation\nof Chemical Methods for Dietary Supplements and Botanicals","author":"AOAC International.","year":"2016"},{"issue":"2","key":"2026083119115851900_cit21","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1177\/000456328902600231","article-title":"Quality Assurance of Hormone Analyses","volume":"26","author":"Bullock","year":"1989","journal-title":"Annals of Clinical Biochemistry"}],"container-title":["ACS Omega"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acsomega.6c03837","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/acsodf\/article-pdf\/11\/33\/49733\/66543023\/acsomega.6c03837.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/acsodf\/article-pdf\/11\/33\/49733\/66543023\/acsomega.6c03837.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T23:12:06Z","timestamp":1788217926000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/acsodf\/article\/11\/33\/49733\/5255250\/PADs-for-a-Safer-Night-s-Sleep-An-Alternative-for"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,14]]},"references-count":21,"journal-issue":{"issue":"33","published-online":{"date-parts":[[2026,8,14]]},"published-print":{"date-parts":[[2026,8,25]]}},"URL":"https:\/\/doi.org\/10.1021\/acsomega.6c03837","relation":{},"ISSN":["2470-1343"],"issn-type":[{"value":"2470-1343","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,14]]}}}