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.

为了研究通过超高效超临界流体色谱-质谱（UHPSFC-MS）分析极性药物和高级制剂辅料在制药行业内，正在开发的分子类型正在发生变化。有一种从基于Lipinski的“五规则”分类的药物分子转移到那些不再适合这种传统方法的分子。在分子（和制剂）设计方面出现了三个值得注意的趋势：1。具有非常低或非常高的疏水性（Log P）的分子，其能够容易地穿透生理膜或增加在作用位点的停留时间2。向更大和更复杂的生物分子实体（例如寡核苷酸、肽、单克隆抗体等）发展。开发用于药物递送的复杂制剂和载体，如脂质体、聚合物纳米颗粒和药物-聚合物缀合物。这些新的药物类型提出了不同的色谱挑战，这些挑战通常无法通过传统方法（如反相HPLC、离子色谱（IC）或尺寸排阻色谱（SEC））解决。SFC的最新进展为选择性鉴定、表征、和极性化合物的定量。SFC还证明了其在分析常用赋形剂的聚合物中的适用性。除了MS检测之外，还可以添加正交检测器，例如ELSD、CLND和CAD，以辅助非发色物质的检测和定量。UHPSFC提供了一种额外的或替代的方法来分析这些新的药物分子，其中反相色谱方法可能具有挑战性。为了实现这种仪器的全部潜力，将需要开发强大的新UHPSFC方法，例如，了解MS电离响应的变化，洗脱液流量分流比，离子抑制问题，除了低水平检测，定量和校准不同的检测器需要探索。