Chewing the fat: How lipidomics is changing our understanding of human health and disease in 2022.

Lipids are biological molecules that play vital roles in all living organisms. They perform many cellular functions, such as 1) forming cellular and subcellular membranes, 2) storing and using energy, and 3) serving as chemical messengers during intra- and inter-cellular signal transduction. The large-scale study of the pathways and networks of cellular lipids in biological systems is called "lipidomics" and is one of the fastest-growing omics technologies of the last two decades. With state-of-the-art mass spectrometry instrumentation and sophisticated data handling, clinical studies show how human lipid composition changes in health and disease, thereby making it a valuable medium to collect for clinical applications, such as disease diagnostics, therapeutic decision-making, and drug development. This review gives a comprehensive overview of current workflows used in clinical research, from sample collection and preparation to data and clinical interpretations. This is followed by an appraisal of applications in 2022 and a perspective on the exciting future of clinical lipidomics.

Dispersant-First Dispersive Liquid-Liquid Microextraction (DF-DLLME), a Novel Sample Preparation Procedure for NDMA Determination in Metformin Products.

Since December 2019, global batch recalls of metformin pharmaceutical products have highlighted an urgent need to control N-nitrosodimethylamine (NDMA) contamination to demonstrate patient safety and maintain supply of this essential medicine. Due to their formulation, the metformin extended-release products present difficult analytical challenges for conventional sample preparation procedures, such as artefactual (in-situ) NDMA formation, gelling, and precipitation. To overcome these challenges, a new version of dispersive liquid-liquid microextraction (DLLME) termed dispersant-first DLLME (DF-DLLME) was developed and optimized for the analysis of NDMA in metformin extended-release products using a detailed Design of Experiments (DoE) to optimize sample preparation. Gas chromatography-high resolution accurate mass-mass spectrometry (GC-HRAM-MS) combined with automated DF-DLLME were successfully applied to monitor the NDMA levels of two different metformin extended-release AstraZeneca products to ultra-trace levels (parts per billion). The additional benefits associated with DF-DLLME, which include automation, time/costs saving, and greener sample preparation, make this novel technique easier to transfer from a development to Quality Control (QC) environment. In addition, this also offers an attractive candidate for the wider platform analysis of N-nitrosamines in pharmaceutical drug products.

Advances in high-resolution mass spectrometry applied to pharmaceuticals in 2020: A whole new age of information.

Continuous improvements in mass spectrometry (MS) have resulted in the widespread availability and adoption of high-resolution mass spectrometry (HRMS) across laboratories worldwide. The capabilities and the associated advantages of HRMS make it an invaluable analytical tool for analyte characterization, screening, and quantification methodologies for a wide scope of applications across pharmaceutical development. These applications include drug discovery, product characterizations of both small molecules and novel drug modalities, in vitro and in vivo metabolism studies, post-approval quality control, and pharmacovigilance. This review gives an overview of the current capabilities of HRMS and its pharmaceutical applications in 2020, and provides a perspective on the future of HRMS within the pharmaceutical industry.