de Souza Israel D, Domingues Diego S, Queiroz Maria E C
Departamento de Química - Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo 14040-901, Brazil.
Departamento de Química - Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo 14040-901, Brazil.
Talanta. 2015 Aug 1;140:166-175. doi: 10.1016/j.talanta.2015.03.032. Epub 2015 Mar 26.
The present study (1) reports on the synthesis of two hybrid silica monoliths functionalized with aminopropyl or cyanopropyl groups by the sol-gel process; (2) evaluates these monoliths as selective stationary phase for microextraction by packed sorbent (MEPS) to determine drugs in plasma samples via liquid chromatography-tandem mass spectrometry (LC-MS/MS) in the multiple reactions monitoring (MRM) mode; and (3) discusses important factors related to the optimization of MEPS efficiency as well as the carryover effect. The prepared hybrid silica monoliths consisted of a uniform, porous, and continuous silica monolithic network. The structure of the aminopropyl hybrid silica monolith was more compact than the structure of the cyanopropyl hybrid silica monolith. The Fourier-transform infrared spectroscopy (FTIR) spectra of the hybrid silica monoliths displayed readily identifiable peaks, characteristic of the cyanopropyl and aminopropyl groups. Compared with the aminopropyl hybrid silica phase, the cyanopropyl hybrid silica phase exhibited higher binding capacity for most of the target drugs. The developed method afforded adequate linearity at concentrations ranging from the lower limit of quantification (0.05-1.00 ng mL(-1)) to the upper limit of quantification (40-10,500 ng mL(-1)); the coefficients of determination (r(2)) were higher than 0.9955. The precision of the method presented coefficients of variation (CV) lower than 14%; the relative standard error (RSE) of the accuracy ranged from -12% to 14%. The developed method allowed for simultaneous analysis of five antipsychotics (olanzapine, quetiapine, clozapine, haloperidol, and chlorpromazine) in combination with seven antidepressants (mirtazapine, paroxetine, citalopram, sertraline, imipramine, clomipramine, fluoxetine), two anticonvulsants (carbamazepine and lamotrigine), and two anxiolytics (diazepam and clonazepam) in plasma samples from schizophrenic patients, which should be valuable for therapeutic drug monitoring purposes.
(1) 报道了通过溶胶 - 凝胶法合成的两种用氨丙基或氰丙基官能化的杂化硅胶整体柱；(2) 评估这些整体柱作为填充吸附剂微萃取（MEPS）的选择性固定相，通过液相色谱 - 串联质谱（LC - MS/MS）在多反应监测（MRM）模式下测定血浆样品中的药物；(3) 讨论了与MEPS效率优化以及残留效应相关的重要因素。制备的杂化硅胶整体柱由均匀、多孔且连续的硅胶整体网络组成。氨丙基杂化硅胶整体柱的结构比氰丙基杂化硅胶整体柱的结构更致密。杂化硅胶整体柱的傅里叶变换红外光谱（FTIR）显示出易于识别的峰，这是氰丙基和氨丙基的特征峰。与氨丙基杂化硅胶相相比，氰丙基杂化硅胶相对大多数目标药物表现出更高的结合能力。所开发的方法在浓度范围从定量下限（0.05 - 1.00 ng mL⁻¹）到定量上限（40 - 10,500 ng mL⁻¹）内具有足够的线性；测定系数（r²）高于0.9955。该方法的精密度变异系数（CV）低于14%；准确度的相对标准误差（RSE）范围为 - 12%至14%。所开发的方法能够同时分析精神分裂症患者血浆样品中的五种抗精神病药物（奥氮平、喹硫平、氯氮平、氟哌啶醇和氯丙嗪）以及七种抗抑郁药物（米氮平、帕罗西汀、西酞普兰、舍曲林、丙咪嗪、氯米帕明、氟西汀）、两种抗惊厥药物（卡马西平和拉莫三嗪）和两种抗焦虑药物（地西泮和氯硝西泮），这对于治疗药物监测目的应该是有价值的。
