Liquid Chromatography-Mass Spectrometry for Clinical Metabolomics: An Overview.

Metabolomics is a discipline that offers a comprehensive analysis of metabolites in biological samples. In the last decades, the notable evolution in liquid chromatography and mass spectrometry technologies has driven an exponential progress in LC-MS-based metabolomics. Targeted and untargeted metabolomics strategies are important tools in health and medical science, especially in the study of disease-related biomarkers, drug discovery and development, toxicology, diet, physical exercise, and precision medicine. Clinical and biological problems can now be understood in terms of metabolic phenotyping. This overview highlights the current approaches to LC-MS-based metabolomics analysis and its applications in the clinical research.

Determination of the Absolute Configuration of Bioactive Indole-Containing Pyrazino[2,1-b]quinazoline-3,6-diones and Study of Their In Vitro Metabolic Profile.

In recent decades, fungi-derived naturally occurring quinazolines have emerged as potential drug candidates. Nevertheless, most studies are conducted for bioactivity assays, and little is known about their absorption, distribution, metabolism, and elimination (ADME) properties. To perform metabolic studies, the synthesis of the naturally occurring quinazolinone, fiscalin B (1), and its chloro derivative, 4-((1H-indol-3-yl)methyl)-8,10-dichloro-1-isobutyl-1,2-dihydro-6H-pyrazino[2,1-b]quinazoline-3,6(4H)-dione (2), disclosed as an antibacterial agent, was performed in a gram scale using a microwave-assisted polycondensation reaction with 22% and 17% yields, respectively. The structure of the non-natural (+)-fiscalin B was established, for the first time, by X-ray crystallography as (1R,4S)-1, and the absolute configuration of the naturally occurring fiscalin B (-)-1 was confirmed by comparison of its calculated and experimental electronic circular dichroism (ECD) spectra as (1S,4R)-1. in vitro metabolic studies were monitored for this class of natural products for the first time by ultra-high-performance liquid chromatography (UHPLC) coupled with high-resolution mass spectrometry (HRMS). The metabolic characteristics of 1 and 2 in human liver microsomes indicated hydration and hydroxylation mass changes introduced to the parent drugs.