Quantification of chemicals in non-targeted analysis without analytical standards - Understanding the mechanism of electrospray ionization and making predictions.

The constant creation and release of new chemicals to the environment is forming an ever-widening gap between available analytical standards and known chemicals. Developing non-targeted analysis (NTA) methods that have the ability to detect a broad spectrum of compounds is critical for research and analysis of emerging contaminants. There is a need to develop methods that make it possible to identify compound structures from their MS and MS/MS information and quantify them without analytical standards. Method refinements that utilize machine learning algorithms and chemical descriptors to estimate the instrument response of particular compounds have made progress in recent years. This narrative review seeks to summarize the current state of the field of non-targeted analysis (NTA) toward quantification of unknowns without the use of analytical standards. Despite the limited accumulation of validation studies on real samples, the ongoing enhancement in data processing and refinement of machine learning tools could lead to more comprehensive chemical coverage of NTA and validated quantitative NTA methods, thus boosting confidence in their usage and enhancing the utility of quantitative NTA.