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: 6107294
• 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: 1999-01-01 至 1999-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6107294
• 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 通过提高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 生物体液中碱性药物的分离。 测定 HPLC 法检测药物目前受到不良和不良因素的限制 有机碱和酸性之间不可重复的分配 硅质烷基修饰载体表面的硅烷醇位点 高效液相色谱柱。 该研究的具体目标有三个。 这 第一个目标是研究和优化实验因素 与二氧化硅进行烷基甲硅烷基化反应，产生具有最大 硅烷负载，可接触的酸性硅烷醇的数量最少 位点和可重复的成分。 研究目的之二 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 了解修改过程和开发 影响更高效键合相的创新策略 基材。 第三个目标是评估 HPLC 性能 烷基硅烷化二氧化硅用于碱性药物混合物的分离。 这 烷基改性二氧化硅的表面组成将被表征 通过漫反射的采集和解释 FTIR 光谱（漂移）。 红外吸收带表示 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。 绝对硅烷表面覆盖度将通过以下方式量化 获得总重量百分比碳数据，其中硅烷 将计算浓度（μmol/m2）。 改性二氧化硅将 装入不锈钢柱和一系列测试混合物中 的基本药物将使用下面的色谱柱进行分析 标准操作条件集。 色谱参数 选择性因子 (alpha)、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，并且 与键合相填充材料的表面结构相关。