Vargas Mena Eleazar, Herrera Giraldo Eliana R, Gómez Castaño Jovanny A
Grupo Ciencias Forenses, Laboratorio de Toxicología Regional de Occidente, Instituto Nacional de Medicina Legal y Ciencias Forenses, Avenida de las Américas No 98-25, Pereira 660004, Colombia.
Grupo Química-Física Molecular y Modelamiento Computacional (QUIMOL), Escuela de Ciencias Químicas, Universidad Pedagógica y Tecnológica de Colombia, Sede Tunja, Avenida Central del Norte, Boyacá 150003, Colombia.
Molecules. 2024 Dec 13;29(24):5884. doi: 10.3390/molecules29245884.
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 ,-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.
硅烷化是一种广泛应用的衍生化技术，用于气相色谱分析苯二氮卓类药物，这类精神活性药物常见于法医和生物样本中。本研究调查了使用含1%三甲基氯硅烷的N,O-双(三甲基硅基)三氟乙酰胺（BSTFA + 1% TMCS）对苯二氮卓类药物进行硅烷化的最佳实验条件，BSTFA + 1% TMCS是一种广泛使用的硅烷化试剂。选择了10种结构不同的苯二氮卓类药物，包括经典的1,4-苯二氮卓核心结构的变体和三唑环衍生物，以研究结构多样性对硅烷化的影响。通过气相色谱-质谱联用（GC-MS）分析，使用主成分分析（PCA）和层次聚类分析（HCA）来优化苯二氮卓类药物的硅烷化。PCA确定了影响硅烷化效率的关键实验因素以及不同苯二氮卓类药物的独特响应模式。HCA根据苯二氮卓类药物的硅烷化行为进一步对其进行分类，突出了定制衍生化策略的必要性。结果表明，BSTFA + 1% TMCS的浓度和溶剂体积对于实现高硅烷化效率至关重要，而温度、反应时间和催化剂的影响较小。优化后的方法成功应用于30个真实的法医样本，证明了其在检测和鉴定各种苯二氮卓类药物（包括依替唑仑等新型毒品）方面的有效性。本研究为改进法医毒理学中的药物检测方法奠定了基础，并为苯二氮卓类药物硅烷化的动力学以及个性化分析参数的使用提供了有用的见解。
