{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T20:46:52Z","timestamp":1790801212660,"version":"4.1.0"},"reference-count":28,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2024,12,13]],"date-time":"2024-12-13T00:00:00Z","timestamp":1734048000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Instituto Nacional de Medicina Legal y Ciencias Forenses in Pereira, Colombia","award":["SGI-3126"],"award-info":[{"award-number":["SGI-3126"]}]},{"name":"Instituto Nacional de Medicina Legal y Ciencias Forenses in Pereira, Colombia","award":["VIE14-2023"],"award-info":[{"award-number":["VIE14-2023"]}]},{"name":"the Universidad Pedag\u00f3gica y Tecnol\u00f3gica de Colombia","award":["SGI-3126"],"award-info":[{"award-number":["SGI-3126"]}]},{"name":"the Universidad Pedag\u00f3gica y Tecnol\u00f3gica de Colombia","award":["VIE14-2023"],"award-info":[{"award-number":["VIE14-2023"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Silylation is a widely used derivatization technique for the gas chromatographic analysis of benzodiazepines, a class of psychoactive drugs commonly encountered in forensic and biological samples. This study investigated the optimal experimental conditions for the silylation of benzodiazepines using N,O-bis(trimethylsilyl)trifluoroacetamide containing 1% trimethylchlorosilane (BSTFA + 1% TMCS), a widely employed silylating agent. Ten structurally different benzodiazepines, including variations within the classic 1,4-benzodiazepine core and triazolo ring derivatives, were selected to address the effect of structural diversity on silylation. Principal component analysis (PCA) and hierarchical cluster analysis (HCA) were used to optimize the silylation of benzodiazepines by means of GC-MS analysis. PCA identified key experimental factors influencing silylation efficiency and distinct response patterns of different benzodiazepines. HCA further categorized the benzodiazepines based on their silylation behavior, highlighting the need for tailored derivatization strategies. The results indicated that the BSTFA + 1% TMCS concentration and solvent volume were pivotal for achieving high silylation efficiency, whereas the temperature, reaction time, and catalyst were less critical. The optimized method was successfully applied to 30 real forensic samples, demonstrating its efficacy in detecting and identifying various benzodiazepines, including designer drugs like etizolam. This study provides a foundation for improving drug detection methodologies in forensic toxicology and provides useful insights into the dynamics of benzodiazepine silylation and the use of individualized analysis parameters.<\/jats:p>","DOI":"10.3390\/molecules29245884","type":"journal-article","created":{"date-parts":[[2024,12,13]],"date-time":"2024-12-13T03:51:08Z","timestamp":1734061868000},"page":"5884","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Insights into the Silylation of Benzodiazepines Using N,O-Bis(trimethylsilyl)trifluoroacetamide (BSTFA): In Search of Optimal Conditions for Forensic Analysis by GC-MS"],"prefix":"10.3390","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9164-4076","authenticated-orcid":false,"given":"Eleazar","family":"Vargas Mena","sequence":"first","affiliation":[{"name":"Grupo Ciencias Forenses, Laboratorio de Toxicolog\u00eda Regional de Occidente, Instituto Nacional de Medicina Legal y Ciencias Forenses, Avenida de las Am\u00e9ricas No 98-25, Pereira 660004, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5592-9632","authenticated-orcid":false,"given":"Eliana R.","family":"Herrera Giraldo","sequence":"additional","affiliation":[{"name":"Grupo Qu\u00edmica-F\u00edsica Molecular y Modelamiento Computacional (QUIMOL), Escuela de Ciencias Qu\u00edmicas, Universidad Pedag\u00f3gica y Tecnol\u00f3gica de Colombia, Sede Tunja, Avenida Central del Norte, Boyac\u00e1 150003, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6654-1315","authenticated-orcid":false,"given":"Jovanny A.","family":"G\u00f3mez Casta\u00f1o","sequence":"additional","affiliation":[{"name":"Grupo Qu\u00edmica-F\u00edsica Molecular y Modelamiento Computacional (QUIMOL), Escuela de Ciencias Qu\u00edmicas, Universidad Pedag\u00f3gica y Tecnol\u00f3gica de Colombia, Sede Tunja, Avenida Central del Norte, Boyac\u00e1 150003, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,13]]},"reference":[{"key":"ref_1","unstructured":"United Nations (2016). 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