A Unifying Review of Bioassay-Guided Fractionation, Effect-Directed Analysis and Related Techniques

Abstract

Abstract:The success of modern methods in analytical chemistry sometimes obscures the problem that the ever increasing amount of analytical data does not necessarily give more insight of practical relevance. As alternative approaches, toxicity-and bioactivity-based assays can deliver valuable information about biological effects of complex materials in humans, other species or even ecosystems. However, the observed effects often cannot be clearly assigned to specific chemical compounds. In these cases, the establishment of an unambiguous cause-effect relationship is not possible. Effect-directed analysis tries to interconnect instrumental analytical techniques with a biological/biochemical entity, which identifies or isolates substances of biological relevance. Successful application has been demonstrated in many fields, either as proof-of-principle studies or even for complex samples. This review discusses the different approaches, advantages and limitations and finally shows some practical examples. The broad emergence of effect-directed analytical concepts might lead to a true paradigm shift in analytical chemistry, away from ever growing lists of chemical compounds. The connection of biological effects with the identification and quantification of molecular entities leads to relevant answers to many real life questions.

Bioassay-coupled Chromatographic Analysis of Medicinal Natural Products: A Review

“…It has the advantage of being associated with high data library which allows tentative identification of compounds. 48 It is not however compatible with many biochemical systems but it has found application in the analysis of fragrance and flavor on GC-olfactometry. 53 …”

“…Disadvantages of LC however includes the use of organic solvents and other additives which are not compatible with most bioassay and fast separation which often do not match the time frame required for many bioassays. 48 Attention is however still on the use of liquid chromatography nuclear magnetic resonance (LC-NMR) and LC-MS (mass spectrometry) for direct and rapid screening of medicinal plant extracts. 49 …”

“…46,47 Liquid Chromatography (LC) Offline and online separation of complex mixtures can be done by Liquid chromatography including Low pressure LC, high performance liquid chromatography (HPLC), ultra-high-performance liquid chromatography (UPLC), counter current chromatography (CCC) and other variants. 48 All these can be coupled with bio-assay and spectroscopy. Disadvantages of LC however includes the use of organic solvents and other additives which are not compatible with most bioassay and fast separation which often do not match the time frame required for many bioassays.…”

BacHBerry: BACterial Hosts for production of Bioactive phenolics from bERRY fruits

“…Semi-preparative chromatography was used to fractionate selected berry extracts with potential bioactive properties using a hybrid approach of bioassay-guided fractionation procedure (Yang et al 2001;Weller 2012;Tayarani-Najaran et al 2013) and screening of pure compounds (Watts et al 2010). Bioassay-guided fractionation typically involves the following steps: assessment of bioactivity, extraction of the biological material with different solvents and testing of bioactivity.…”

At-Line Cellular Screening Methodology for Bioactives in Mixtures Targeting the α7-Nicotinic Acetylcholine Receptor

“…This traditional approach often is called bioassay-guided fractionation or-in environmental settingseffect-directed analysis. 7,8 On-line screening is the technique with the shortest overall analysis times, but many bioassays cannot be implemented in an on-line format, such as bioassays with long incubation times, cellular bioassays, and radioligand binding assays. At-line screening methodologies were developed, allowing application of bioassays separate from the time and place of the LC-MS experiment.…”