{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T10:25:46Z","timestamp":1770891946353,"version":"3.50.1"},"reference-count":31,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2024,9,2]],"date-time":"2024-09-02T00:00:00Z","timestamp":1725235200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"LEPABE","award":["UIDB\/00511\/2020"],"award-info":[{"award-number":["UIDB\/00511\/2020"]}]},{"name":"LEPABE","award":["UIDP\/00511\/20200"],"award-info":[{"award-number":["UIDP\/00511\/20200"]}]},{"name":"LEPABE","award":["LA\/P\/0045\/2020"],"award-info":[{"award-number":["LA\/P\/0045\/2020"]}]},{"name":"LEPABE","award":["EXPL\/NAN-MAT\/0209\/2021"],"award-info":[{"award-number":["EXPL\/NAN-MAT\/0209\/2021"]}]},{"name":"LEPABE","award":["D.N. (UI\/BD\/150946\/2021)"],"award-info":[{"award-number":["D.N. (UI\/BD\/150946\/2021)"]}]},{"name":"ALiCE","award":["UIDB\/00511\/2020"],"award-info":[{"award-number":["UIDB\/00511\/2020"]}]},{"name":"ALiCE","award":["UIDP\/00511\/20200"],"award-info":[{"award-number":["UIDP\/00511\/20200"]}]},{"name":"ALiCE","award":["LA\/P\/0045\/2020"],"award-info":[{"award-number":["LA\/P\/0045\/2020"]}]},{"name":"ALiCE","award":["EXPL\/NAN-MAT\/0209\/2021"],"award-info":[{"award-number":["EXPL\/NAN-MAT\/0209\/2021"]}]},{"name":"ALiCE","award":["D.N. (UI\/BD\/150946\/2021)"],"award-info":[{"award-number":["D.N. (UI\/BD\/150946\/2021)"]}]},{"name":"FCT\/MCTES (PIDDAC)","award":["UIDB\/00511\/2020"],"award-info":[{"award-number":["UIDB\/00511\/2020"]}]},{"name":"FCT\/MCTES (PIDDAC)","award":["UIDP\/00511\/20200"],"award-info":[{"award-number":["UIDP\/00511\/20200"]}]},{"name":"FCT\/MCTES (PIDDAC)","award":["LA\/P\/0045\/2020"],"award-info":[{"award-number":["LA\/P\/0045\/2020"]}]},{"name":"FCT\/MCTES (PIDDAC)","award":["EXPL\/NAN-MAT\/0209\/2021"],"award-info":[{"award-number":["EXPL\/NAN-MAT\/0209\/2021"]}]},{"name":"FCT\/MCTES (PIDDAC)","award":["D.N. (UI\/BD\/150946\/2021)"],"award-info":[{"award-number":["D.N. (UI\/BD\/150946\/2021)"]}]},{"name":"FCT","award":["UIDB\/00511\/2020"],"award-info":[{"award-number":["UIDB\/00511\/2020"]}]},{"name":"FCT","award":["UIDP\/00511\/20200"],"award-info":[{"award-number":["UIDP\/00511\/20200"]}]},{"name":"FCT","award":["LA\/P\/0045\/2020"],"award-info":[{"award-number":["LA\/P\/0045\/2020"]}]},{"name":"FCT","award":["EXPL\/NAN-MAT\/0209\/2021"],"award-info":[{"award-number":["EXPL\/NAN-MAT\/0209\/2021"]}]},{"name":"FCT","award":["D.N. (UI\/BD\/150946\/2021)"],"award-info":[{"award-number":["D.N. (UI\/BD\/150946\/2021)"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Memantine, a non-competitive NMDA receptor antagonist, is used to treat Alzheimer\u2019s disease. Therefore, loading memantine in nanoparticles (NPs) could be an essential tool to improve the treatment effectiveness while reducing drug toxicity. Even though some approaches have been described to quantify memantine, none reported optimized methods using high-performance liquid chromatography resorting to ultraviolet detection (UV\u2013HPLC) to determine encapsulation in NPs. The present research developed a HPLC method using pre-column derivatization for quantitatively analyzing memantine hydrochloride in NPs. Memantine was derivatized using 9-fluorenylmethyl chloroformate (FMOC). The developed method was fully validated regarding suitability, specificity, linearity, sensitivity, precision, accuracy, and robustness according to the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use guidelines. The retention time of memantine was 11.393 \u00b1 0.003 min, with a mean recovery of 92.9 \u00b1 3.7%. The new chromatographic method was validated and found to respond linearly over 5\u2013140 \u03bcg\/mL, with a high coefficient of determination. Intraday precision lay between 3.6% and 4.6%, and interday precision between 4.2% and 9.3%. The stability of memantine was also tested at 4 \u00b0C and \u221220 \u00b0C, and no signs of decay were found for up to 6 months. The new method was properly validated and proved simple, sensitive, specific, accurate, and precise for determining memantine encapsulation efficiency in lipid NPs. Greenness was evaluated, presenting a final score of 0.45. In the future, this methodology could also be applied to quantify memantine in different nanoformulations.<\/jats:p>","DOI":"10.3390\/ph17091162","type":"journal-article","created":{"date-parts":[[2024,9,2]],"date-time":"2024-09-02T06:51:17Z","timestamp":1725259877000},"page":"1162","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Development and Validation of a Simple UV\u2013HPLC Method to Quantify the Memantine Drug Used in Alzheimer\u2019s Treatment"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9680-8765","authenticated-orcid":false,"given":"D\u00e9bora","family":"Nunes","sequence":"first","affiliation":[{"name":"LEPABE\u2014Laboratory for Process Engineering, Environment, Biotechnology and Energy, Faculty of Engineering, University of Porto, Rua Dr. Roberto Frias, 4200-465 Porto, Portugal"},{"name":"ALiCE\u2014Associate Laboratory in Chemical Engineering, Faculty of Engineering, University of Porto, Rua Dr. Roberto Frias, 4200-465 Porto, Portugal"}]},{"given":"T\u00e2nia G.","family":"Tavares","sequence":"additional","affiliation":[{"name":"LEPABE\u2014Laboratory for Process Engineering, Environment, Biotechnology and Energy, Faculty of Engineering, University of Porto, Rua Dr. Roberto Frias, 4200-465 Porto, Portugal"},{"name":"ALiCE\u2014Associate Laboratory in Chemical Engineering, Faculty of Engineering, University of Porto, Rua Dr. Roberto Frias, 4200-465 Porto, Portugal"}]},{"given":"Frenacisco Xavier","family":"Malcata","sequence":"additional","affiliation":[{"name":"LEPABE\u2014Laboratory for Process Engineering, Environment, Biotechnology and Energy, Faculty of Engineering, University of Porto, Rua Dr. Roberto Frias, 4200-465 Porto, Portugal"},{"name":"ALiCE\u2014Associate Laboratory in Chemical Engineering, Faculty of Engineering, University of Porto, Rua Dr. Roberto Frias, 4200-465 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9841-3967","authenticated-orcid":false,"given":"Joana A.","family":"Loureiro","sequence":"additional","affiliation":[{"name":"LEPABE\u2014Laboratory for Process Engineering, Environment, Biotechnology and Energy, Faculty of Engineering, University of Porto, Rua Dr. Roberto Frias, 4200-465 Porto, Portugal"},{"name":"ALiCE\u2014Associate Laboratory in Chemical Engineering, Faculty of Engineering, University of Porto, Rua Dr. Roberto Frias, 4200-465 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8505-3432","authenticated-orcid":false,"given":"Maria Carmo","family":"Pereira","sequence":"additional","affiliation":[{"name":"LEPABE\u2014Laboratory for Process Engineering, Environment, Biotechnology and Energy, Faculty of Engineering, University of Porto, Rua Dr. Roberto Frias, 4200-465 Porto, Portugal"},{"name":"ALiCE\u2014Associate Laboratory in Chemical Engineering, Faculty of Engineering, University of Porto, Rua Dr. Roberto Frias, 4200-465 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Liu, J., Chang, L., Song, Y., Li, H., and Wu, Y. (2019). The Role of NMDA Receptors in Alzheimer\u2019s Disease. Front. Neurosci., 13.","DOI":"10.3389\/fnins.2019.00043"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1016\/j.neuropharm.2007.07.013","article-title":"Memantine: A NMDA receptor antagonist that improves memory by restoration of homeostasis in the glutamatergic system\u2014Too little activation is bad, too much is even worse","volume":"53","author":"Parsons","year":"2007","journal-title":"Neuropharmacology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1547","DOI":"10.1002\/cphc.202100124","article-title":"The Role of Amyloid \u03b2-Biomembrane Interactions in the Pathogenesis of Alzheimer\u2019s Disease: Insights from Liposomes as Membrane Models","volume":"22","author":"Andrade","year":"2021","journal-title":"ChemPhysChem"},{"key":"ref_4","first-page":"569","article-title":"Progress update: Pharmacological treatment of Alzheimer\u2019s disease","volume":"3","author":"Hogan","year":"2007","journal-title":"Neuropsychiatr. Dis. Treat."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.ejphar.2017.02.001","article-title":"Memantine reduces the production of amyloid-\u03b2 peptides through modulation of amyloid precursor protein trafficking","volume":"798","author":"Ito","year":"2017","journal-title":"Eur. J. Pharmacol."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Matsunaga, S., Kishi, T., and Iwata, N. (2015). Memantine monotherapy for Alzheimer\u2019s disease: A systematic review and meta-analysis. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0123289"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1007\/s12035-020-02120-z","article-title":"Chronic Memantine Treatment Ameliorates Behavioral Deficits, Neuron Loss, and Impaired Neurogenesis in a Model of Alzheimer\u2019s Disease","volume":"58","author":"Stazi","year":"2021","journal-title":"Mol. Neurobiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1016\/j.jconrel.2020.05.041","article-title":"Nanoparticle-hydrogel superstructures for biomedical applications","volume":"324","author":"Jiang","year":"2020","journal-title":"J. Control. Release"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Begines, B., Ortiz, T., P\u00e9rez-Aranda, M., Mart\u00ednez, G., Merinero, M., Arg\u00fcelles-Arias, F., and Alcudia, A. (2020). Polymeric Nanoparticles for Drug Delivery: Recent Developments and Future Prospects. Nanomaterials, 10.","DOI":"10.3390\/nano10071403"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1097\/FTD.0b013e31821126cf","article-title":"Simultaneous determination of antidementia drugs in human plasma for therapeutic drug monitoring","volume":"33","author":"Noetzli","year":"2011","journal-title":"Ther. Drug Monit."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.1007\/s40262-018-0632-y","article-title":"Clinical Pharmacokinetics and Pharmacodynamics of Drugs in the Central Nervous System","volume":"57","author":"Srinivas","year":"2018","journal-title":"Clin. Pharmacokinet."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1365\/s10337-009-1231-8","article-title":"Determination of Memantine in Human Plasma by LC\u2013MS\u2013MS: Application to a Pharmacokinetic Study","volume":"70","author":"Pan","year":"2009","journal-title":"Chromatographia"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.jpba.2012.02.008","article-title":"Simultaneous determination of antidementia drugs in human plasma: Procedure transfer from HPLC\u2013MS to UPLC\u2013MS\/MS","volume":"64\u201365","author":"Noetzli","year":"2012","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1007\/s40005-015-0184-1","article-title":"Validation and application of a simple reverse phase HPLC method for in vitro dissolution studies of memantine hydrochloride tablet","volume":"45","author":"Maeng","year":"2015","journal-title":"J. Pharm. Investig."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"105331","DOI":"10.1016\/j.ejps.2020.105331","article-title":"Nanoporous microneedle arrays seamlessly connected to a drug reservoir for tunable transdermal delivery of memantine","volume":"150","author":"Vos","year":"2020","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3482","DOI":"10.1002\/jssc.202000592","article-title":"Development of a novel, fast, simple, nonderivative HPLC method with direct UV measurement for quantification of memantine hydrochloride in tablets","volume":"43","author":"Piponski","year":"2020","journal-title":"J. Sep. Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"672183","DOI":"10.1155\/2015\/672183","article-title":"HPLC-Fluorescent Analysis of Memantine: An Investigation on Fluorescent Derivative Formation","volume":"2015","author":"Prapatpong","year":"2015","journal-title":"J. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.jchromb.2015.09.016","article-title":"A new simultaneous derivatization and microextration method for the determination of memantine hydrochloride in human plasma","volume":"1008","author":"Jing","year":"2016","journal-title":"J. Chromatogr. B Anal. Technol. Biomed. Life Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1431","DOI":"10.1002\/bmc.3116","article-title":"Review of the validated HPLC and LC-MS\/MS methods for determination of drugs used in clinical practice for Alzheimer\u2019s disease","volume":"28","author":"Sharma","year":"2014","journal-title":"Biomed. Chromatogr."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"37","DOI":"10.4137\/ACI.S3936","article-title":"A Validated Stability-indicating Reverse Phase HPLC Assay Method for the Determination of Memantine Hydrochloride Drug Substance with UV-Detection Using Precolumn Derivatization Technique","volume":"5","author":"Narola","year":"2010","journal-title":"Anal. Chem. Insights"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1097\/FTD.0b013e31826933ab","article-title":"Implementation of a cost-effective HPLC\/UV approach for routine medical quantification of memantine in human serum","volume":"34","author":"Haen","year":"2012","journal-title":"Ther. Drug Monit."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"502652","DOI":"10.1155\/2013\/502652","article-title":"High-Performance Liquid Chromatographic Ultraviolet Determination of Memantine Hydrochloride after In Vitro Transdermal Diffusion Studies","volume":"2013","author":"Merino","year":"2013","journal-title":"J. Chem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"847","DOI":"10.3797\/scipharm.1008-17","article-title":"Sensitive and rapid HPLC method for determination of memantine in human plasma using OPA derivatization and fluorescence detection: Application to pharmacokinetic studies","volume":"78","author":"Zarghi","year":"2010","journal-title":"Sci. Pharm."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1302","DOI":"10.5740\/jaoacint.11-080","article-title":"High-Performance Liquid Chromatographic Determination of Memantine in Human Urine Following Solid-Phase Extraction and Precolumn Derivatization","volume":"96","author":"Michail","year":"2013","journal-title":"J. AOAC Int."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1002\/bmc.1648","article-title":"Determination of memantine in rat plasma by HPLC-fluorescence method and its application to study of the pharmacokinetic interaction between memantine and methazolamide","volume":"26","author":"Hassan","year":"2012","journal-title":"Biomed. Chromatogr."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1093\/chrsci\/49.10.745","article-title":"Determination of memantine in plasma and vitreous humour by HPLC with precolumn derivatization and fluorescence detection","volume":"49","author":"Puente","year":"2011","journal-title":"J. Chromatogr. Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1002\/jssc.201000579","article-title":"High-performance liquid chromatographic determination of memantine hydrochloride in rat plasma using sensitive fluorometric derivatization","volume":"34","author":"Xie","year":"2011","journal-title":"J. Sep. Sci."},{"key":"ref_28","unstructured":"European Medicines Agency (EMA) (2005). ICH Q2(R1): Validation of Analytical Procedures: Text and methodology, International Conference on Harmonization (ICH) of Technical Requirements for the Registration of Pharmaceuticals for Human Use, Geneva, Switzerland."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1007\/s10337-022-04160-0","article-title":"Development and Validation of a Simple, Selective, and Accurate Reversed-Phase Liquid Chromatographic Method with Diode Array Detection (RP-HPLC\/DAD) for the Simultaneous Analysis of 18 Free Amino Acids in Topical Formulations","volume":"85","author":"Kahsay","year":"2022","journal-title":"Chromatographia"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1166\/jnn.2014.9119","article-title":"Nanoparticles and Blood-Brain Barrier: The Key to Central Nervous System Diseases","volume":"14","author":"Cerio","year":"2014","journal-title":"J. Nanosci. Nanotechnol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"10076","DOI":"10.1021\/acs.analchem.0c01887","article-title":"AGREE\u2014Analytical GREEnness Metric Approach and Software","volume":"92","author":"Wojnowski","year":"2020","journal-title":"Anal. Chem."}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/17\/9\/1162\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:47:13Z","timestamp":1760111233000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/17\/9\/1162"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,2]]},"references-count":31,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2024,9]]}},"alternative-id":["ph17091162"],"URL":"https:\/\/doi.org\/10.3390\/ph17091162","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,2]]}}}