Strategies for the Quantification of Endogenously Present Small Molecules in Biological Samples

The quantification of endogenously present compounds in biological samples demands appropriately validated methods, in particular because increasing research efforts are aimed at studying the impact of such compounds on human health and disease. International regulatory agencies, such as the Food and Drug Administration (FDA) and the European Medicine Agency (EMA), have published a vast number of guidelines concerning bioanalytical method validation over recent decades. Compared with the quantification of exogenous compounds, these guidelines have remained rather vague and unclear when it comes to the quantification of endogenous compounds. Nonetheless, the continuous expansion of studies devoted to the search for endogenous disease markers in the human metabolome has incited the regulatory bodies to include endogenous compounds in a draft of an updated International Conference on Harmonization (ICH) guideline on bioanalytical method validation. In light of these recent developments, the main objective of this review article is to provide a clear summary of the different methods that can be used to quantify endogenous small molecules. Because of the increased use of mass spectrometry (MS) in the field of bioanalysis, a special focus will be placed on quantification by liquid chromatography (LC)–MS. Practical recommendations to face this bioanalytical challenge, in particular in terms of method validation, will also be provided.

Publication year:2019

BOF-keylabel:yes

IOF-keylabel:yes

BOF-publication weight:0.1

CSS-citation score:1

Authors from:Higher Education

Accessibility:Open