BONDED PHASE SUBSTRATES FOR HPLC ANALYSIS OF BASIC PHARMACEUTICALS

用于基础药物 HPLC 分析的键合相基质

• 批准号: 6271652
• 负责人: KRISTINE G PROCTOR
• 金额: $ 8.18万
• 依托单位: COLORADO STATE UNIVERSITY-PUEBLO
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-01-01 至 1998-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6271652
• 关键词: chemical kinetics; drug /agent; fluid; high performance liquid chromatography; infrared spectrometry; interferometry; physical separation; silicates; thermostability

The long range objective of the project is to broadly advance biomedical research by improving the performance of bonded phase substrates in the high performance liquid chromatographic (HPLC) separation of basic drugs inbiological fluids. Determinations of pharmaceuticals by HPLC is currently limited by undesirable and irreproducible partitioning between the organic base and acidic silanol sites on the surface of siliceous alkylmodified supports in HPLC columns. The specific aims of the research are three-fold. The first aim is to study and optimize experimental factors of the alkylsilylation reaction with silica, to yield surfaces with maximum silane laoding, minimal number of accessible and acidic silanol sites, and reproducible composition. The second aim of the research is to study the kinetics of the silylation reaction insolution and gaseous phases. Results of these studies will contribute to a better understanding of the modification process and the development of innovative strategies to affect a more efficient bonded phase substrate. The third aim is to assess the HPLC performance of alkylsilylated silicas in separations of basic drug mixtures. The surface composition of alkylmodified silicas will be characterized through the acquisition and interpretation of diffuse reflectance FTIR spectra (DRIFTS). Infrared absorption bands indicative of unreacted silanol sites (3743 cm-1) and the attached alkyl reagent (2900 cm-1) will be used to assess the extent of the silylation reaction. Absolute silane surface coverage will be quantified by obtaining total weight percentage carbon data from which silane concentration (mumol/m2) will be calculated. Modified silicas will be packed into stainless steel columns and a series of test mixtures of basic pharmaceuticals will be analyzed using the columns under a standard set of operating conditions. Chromatographic parameters of selectivity factor (alpha), peak asymmetry (A), capacity factor (k'), theoretical plates (N) and column stability will be assessed, and correlated to surface structure of bonded phase packing materials.

该项目的长期目标是广泛推进 改善键合相性能的生物医学研究 高效液相色谱中的底物 生物体液中基本药物的分离。有关的决定 高效液相色谱检测的药物目前受到不良和 在有机碱和酸性之间不可重现的分配 硅烷基改性载体表面的硅醇中心 高效液相色谱柱。研究的具体目的有三个方面。这个 第一个目标是研究和优化实验因素。 与二氧化硅的烷基硅基化反应，得到最大值的表面 硅烷装填，可接近的最低数量的酸性硅醇 站点和可复制的构图。研究的第二个目的 是研究溶液中硅烷化反应的动力学， 气相。这些研究的结果将有助于更好地 对改装过程和发展的理解 影响更有效的保税阶段的创新战略 底物。第三个目标是评估高效液相色谱性能 烷基硅烷基硅酸盐用于基本药物混合物的分离。这个 烷基改性二氧化硅的表面组成将被表征 通过获取和解释漫反射比 FTIR光谱(漂移)。红外吸收带表明 未反应的硅醇中心(3743 cm-1)和附着的烷基试剂 (2900 cm-1)将用于评估硅基化的程度 反应。硅烷表面的绝对覆盖率将通过以下方式进行量化 获取硅烷的总重量百分比碳数据 浓度(摩尔/平方米)将被计算出来。改性二氧化硅将 填充在不锈钢柱和一系列测试混合物中 基本药物的分析将使用 一套标准的运行条件。色谱学参数 选择性因子(α)、峰不对称性(A)、容量因子(k‘)、 将评估理论板(N)和柱的稳定性，以及 与粘结相填充材料的表面结构相关。