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: 6217811
• 负责人: KRISTINE G PROCTOR
• 金额: $ 5.86万
• 依托单位: COLORADO STATE UNIVERSITY-PUEBLO
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-30 至 1999-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6217811
• 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促进 通过改善键合相的性能进行生物医学研究 高效液相色谱（HPLC）中的底物 分离生物液体中的基本药物。 的确定 目前，通过HPLC测定药物的方法受到不期望的和 在有机碱和酸之间的不可再生的分配 硅烷基改性载体表面上的硅烷醇位点， HPLC色谱柱。 研究的具体目标有三个方面。 的 目的是研究和优化实验条件， 与二氧化硅的烷基硅烷化反应，以产生具有最大 硅烷涂覆，最小数量的可接近的酸性硅烷醇 网站和可重复的组成。 研究的第二个目的 研究了溶液中硅烷化反应的动力学， 气相 这些研究结果将有助于更好地 了解改性过程和发展 创新战略，以实现更有效的保税阶段 衬底 第三个目的是评估HPLC性能， 烷基甲硅烷基化的二氧化硅在分离基本药物混合物中的应用。 的 将表征烷基改性二氧化硅表面组成 通过获取和解释漫反射率 FTIR光谱（DRIFTS）。 红外吸收带表明 未反应的硅烷醇位点（3743 cm-1）和连接的烷基试剂 (2900 cm-1）将用于评估甲硅烷基化的程度 反应 绝对硅烷表面覆盖率将通过以下方式量化： 获得总重量百分比碳数据， 计算浓度（mumol/m2）。 改性二氧化硅将 将其装入不锈钢柱中， 基本药物的分析将使用 标准的操作条件。 色谱参数 选择性因子（α），峰不对称性（A），容量因子（k ′）， 将评估理论塔板数（N）和色谱柱稳定性， 与键合相填料的表面结构有关。