Rapid advances have been made in developing analytical technologies for characterization of highly heterogeneous active ingredients of complex drugs, such as pentosan polysulfate (PPS), active ingredient of the drug Elmiron®, approved by the Food and Drug Administration and marketed in the United States to treat interstitial cystitis. PPS sulfated polysaccharides comprise of a repeat unit of β(1-4)-D-xylopyranoses randomly substituted by 4-O-methyl-glucopyranosyluronic acid. To define the critical quality attributes (CQAs) of such a complex drug, it is critical to develop an approach that integrates data from orthogonal analytical methodologies. Here, we developed an approach integrating diverse analytical tools including gel permeation chromatography, LC/ESI-MS and NMR to measure CQAs of PPS. The proposed mathematical framework integrates the data from these diverse analytical methods as function of PPS chain length and building blocks. Our approach would facilitate in establishing a scientific foundation for comparative characterization of drug products with complex active ingredients.

中文翻译：

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使用正交分析工具对戊聚糖多硫酸钠钠复合药物进行深入的结构表征。

在开发用于表征复杂药物的高度异质活性成分的分析技术方面取得了快速进展，例如戊三聚糖多硫酸盐（PPS），Elmiron®药物的活性成分，已获得美国食品药品监督管理局（FDA）批准并在美国销售。治疗间质性膀胱炎。PPS硫酸化多糖包含被4-O-甲基-吡喃葡糖基糖醛酸随机取代的β（1-4）-D-吡喃木糖的重复单元。为了定义这种复杂药物的关键质量属性（CQA），开发一种整合正交分析方法数据的方法至关重要。在这里，我们开发了一种方法，该方法集成了包括凝胶渗透色谱法，LC / ESI-MS和NMR在内的多种分析工具来测量PPS的CQA。拟议的数学框架将来自这些不同分析方法的数据整合为PPS链长和构件的函数。我们的方法将有助于为具有复杂有效成分的药物产品的比较表征建立科学基础。