{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T20:49:16Z","timestamp":1791406156836,"version":"4.3.3"},"reference-count":26,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2024,11,23]],"date-time":"2024-11-23T00:00:00Z","timestamp":1732320000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>In recent years, the detection of nitrosamine precursors has become an important issue for regulatory authorities such as the European Medicines Agency (EMA) and the Food and Drug Administration (FDA). The present study provides a pre-column derivatization method for the analysis of dimethylamine (DMA) and diethylamine (DEA) in pharmaceutical products using HPLC and a fluorescence detector. Appropriate chromatographic parameters, including mobile phase composition (organic solvent, buffer, pH), elution type, flow rate, temperature, and \u03bbexcitation\/emission, were investigated. Analysis was performed at \u03bbexcitation = 450 nm and \u03bbemission = 540 nm on a C18 column (at 40 \u00b0C) using gradient elution as a mobile phase with Eluent A: Phosphoric Acid Buffer (20 mM, pH = 2.8) and Eluent B: methanol, with a flow of 0.8 mL\/min. The method was validated according to ICH specifications in terms of linearity (0.5\u201310 ng\/mL for DMA and 5\u2013100 ng\/mL for DEA), specificity, and robustness, as well as repeatability, intermediate precision (%RSD &lt; 2.9), and accuracy (% recovery 98.2\u2013102.0%). The derivatization process was optimized using the \u201cCrossed D-Optimal\u201d experimental design procedure, where one mixture component was cross-correlated with two factors. The stability of the samples was studied over a period of one month. To process the samples (pharmaceuticals), various purification techniques were tried using solid\/liquid or liquid\/liquid extraction with dichloromethane. Finally, a straightforward solid-phase extraction (SPE, C18) method was chosen prior to derivatization. The method was successfully applied, since the extraction recoveries were &gt;81.6% for DMA (0.5 ppm) and &gt;81.1% for DEA (5 ppm). Based on the results obtained and the available literature, the scientific community seeks, by proposing flexible analytical methods, to delimit the problem of nitrosamines.<\/jats:p>","DOI":"10.3390\/molecules29235535","type":"journal-article","created":{"date-parts":[[2024,11,25]],"date-time":"2024-11-25T08:38:24Z","timestamp":1732523904000},"page":"5535","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["A Pre-Column Derivatization Method for the HPLC-FLD Determination of Dimethyl and Diethyl Amine in Pharmaceuticals"],"prefix":"10.3390","volume":"29","author":[{"given":"Georgios","family":"Kamaris","sequence":"first","affiliation":[{"name":"Laboratory of Pharmaceutical Analysis, Department of Pharmacy, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Tsami","sequence":"additional","affiliation":[{"name":"Laboratory of Pharmaceutical Analysis, Department of Pharmacy, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgiana-Roxana","family":"Lotca","sequence":"additional","affiliation":[{"name":"Laboratory of Pharmaceutical Analysis, Department of Pharmacy, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofia","family":"Almpani","sequence":"additional","affiliation":[{"name":"Laboratory of Pharmaceutical Analysis, Department of Pharmacy, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine K.","family":"Markopoulou","sequence":"additional","affiliation":[{"name":"Laboratory of Pharmaceutical Analysis, Department of Pharmacy, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Jire\u0161, J., Dou\u0161a, M., Gibala, P., and Kubelka, T. 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