Fourier transform ion cyclotron resonance mass spectrometry for the analysis of molecular composition and batch-to-batch consistency of plant-derived polyphenolic ligands developed for biomedical application.

Unlabelled: Complex plant-derived polyphenols are promising for biomedical application. Their high complexity prevents the use of conventional pharmacopoeia techniques to perform quality control. The goal of this study was to apply ultra-high-resolution mass spectrometry to evaluate the batch-to-batch consistency of the molecular composition of a polyphenolic ligand using appropriate statistical metrics.

Methods: Polyphenols were obtained by hydrolyzed-lignin oxidation. Manufacturing was performed under a range of reaction conditions: heating cycles, oxygen flows, purification. Direct-injection Fourier transform ion cyclotron resonance mass spectrometry (DI FTICR-MS) was applied to analyze reaction products. For pairwise comparison Jaccard and Tanimoto similarities calculations were proposed. In addition, principal component analysis (PCA) was applied for sample grouping based on the molecular class contributions.

Results: FTICR-MS analysis revealed moderate Jaccard similarity of products synthesized under the same conditions, which shared about 50% of the formulae calculated in each sample. The intensity-based Tanimoto index indicated high similarity of major components distribution of samples synthesized under standard conditions, while products obtained with variations in synthetic conditions were significantly different. PCA of molecular class contributions showed similar grouping with a high cumulative score.

Conclusions: FTICR-MS provides robust metrics for the examination of batch-to-batch consistency of synthetic polyphenol materials. This approach can be proposed for the analysis of reference samples and for development of complementary methods for quality control of medicinal agents based on various biologically active matrices.