Combining the Strengths of MS and NMR in Biochemometrics: A Case Study on <i>Buddleja officinalis</i>

Biochemometrics has emerged as promising strategy for the targeted identification of bioactive constituents from natural sources. It is based on the correlation of bioactivity data with chemical data to reveal constituents contributing to activity. Providing complementary data and structural information, MS- and NMR-based biochemometric approaches have both been separately applied in the past. The herein presented study is dedicated to the evaluation of a combined MS- and NMR-based biochemometric workflow for the unambiguous identification of bioactives. As an example, a flower extract of <i>Buddleja officinalis</i> Maxim. was selected to unravel bioactive constituents in the context of dry eye disease pathology. While NMR-based biochemometrics relies on heterocovariance analysis (HetCA) of ¹H NMR spectra using the previously established ELINA approach, a biochemometric molecular network was generated for the MS-based approach. Both analyses were performed in parallel and were ultimately combined to increase their power to identify the bioactive constituents from the complex mixture. As a result, phenylethanoid glycosides and triterpene saponins were discovered as main contributors for the antioxidant and cytotoxic effects of the extract. This article illustrates the advantages, opportunities, and limitations of MS and NMR in the context of biochemometrics.