Analysis of Polar Drug Molecules and Excipients by Ultrahigh Performance Supercritical Fluid Chromatography - Mass Spectrometry

采用超高性能超临界流体色谱-质谱法分析极性药物分子和赋形剂

• 批准号: 2100676
• 金额: --
• 依托单位: University of Southampton
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2018
• 资助国家: 英国
• 起止时间: 2018 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2100676
• 关键词: Analysis; Polar; Drug; Molecules; Excipients

To investigate the analysis of polar drugs and advanced formulation excipients by Ultrahigh Performance Supercritical Fluid Chromatography - Mass Spectrometry (UHPSFC-MS) Within the pharmaceutical industry, an evolution in the types of molecules being developed is underway. There is a move from drugable molecules based on Lipinski's 'Rule of Five' classification to those that no longer fit this traditional approach. There are three notable trends emerging in terms of molecular (and formulation) design:1. Molecules with very low or very high hydrophobicity (Log P) that enable facile penetration through physiological membranes or increased residence time at site of action 2. A move towards larger and more complex biomolecular entities, e.g. oligonucleotides, peptides, mAbs etc.3. Development of complex formulations and vehicles for drug delivery such as liposomes, polymer nanoparticles and drug-polymer conjugates.These new drug types pose different chromatographic challenges that are often not resolvable via traditional approaches such as reversed-phase HPLC, ion chromatography (IC) or size exclusion chromatography (SEC).Recent advances in SFC have opened the way to selective identification, characterisation, and quantification of polar compounds. SFC has also demonstrated its applicability in for the analysis of polymers commonly used as excipients. In addition to MS detection, orthogonal detectors, e.g. ELSD, CLND and CAD can be added to aid detection and quantification of non-chromophoric materials. UHPSFC offers an additional, or alternative approach to analysis of some of these new drug molecules where reversed-phase chromatographic approaches can be challenging. To realise the full potential of this instrumentation the development of robust new UHPSFC methodologies will be required, e.g. Understanding the changes in MS ionisation response, eluent flow split ratio, ion suppression issues, in addition to low level detection, quantification and calibration with different detectors requires exploration.

为了通过超高性能超临界流体色谱法 - 质谱（UHPSFC -MS）在制药行业中对极性药物和晚期制剂赋形剂进行分析，正在开发的分子类型的演变正在进行中。从基于Lipinski的“五个规则”分类的可吸毒分子转变为不再适合这种传统方法的分子的转变。在分子（和配方）设计方面，出现了三种显着的趋势：1。具有非常低或非常高的疏水性（log p）的分子，可以通过生理膜易于渗透或在作用部位2的停留时间。寡核苷酸，肽，mAb等3。开发复杂的配方和用于药物输送的车辆，例如脂质体，聚合物纳米颗粒和药物聚合物偶联物。这些新药构成了不同的色谱挑战，这些挑战通常无法通过传统方法（例如反相 - 阶段HPLC，ION HPLC），离子离子（IC）或离子（IC）或IC SFC的尺寸排除色谱法（SEC）的进展为极性化合物的选择性识别，表征和定量开辟了道路。 SFC还证明了其用于分析通常用作赋形剂的聚合物的适用性。除了MS检测外，正交检测器，例如可以添加ELSD，CLND和CAD来帮助检测和定量非肉眼材料。 UHPSFC提供了另一种或替代方法来分析这些新药分子中的某些分子，在这些新药分子中，相反的阶段色谱方法可能具有挑战性。为了实现这种仪器的全部潜力，将需要强大的新UHPSFC方法的发展，例如除了低水平检测，使用不同检测器的校准外，还需要探索MS电离响应，洗脱液流动比，离子抑制问题的变化，离子抑制问题。