Oligonucleotides—therapeutic agents for difficult-to-treat diseases—rely on precise molecular weight confirmation to ensure quality during development. Experts from Agilent Technologies explore the challenges of liquid chromatography-mass spectrometry (LC/MS) analysis in oligonucleotide synthesis, as well as strategies for accurate deconvolution, method development, and optimal equipment selection.
Direct Analysis of Class 2 Residual Solvents Using Molecular Rotational Resonance Spectroscopy
February 19th 2025Molecular rotational resonance (MRR) spectroscopy operates in the microwave region, detecting transitions between pure rotational energy levels. Combined with adiabatic cooling, MRR produces highly selective spectra unique to each molecule’s atomic structure. Even slight changes in atomic position or mass result in distinct spectral differences, allowing MRR to directly analyze complex mixtures, including isomers, without chromatographic separation. This article presents a continuous headspace-MRR method for analyzing Class 2 residual solvents, including low-volatility solvents from Class 2 Mixture C. By evaluating solvents with diverse boiling points, the study demonstrates that MRR meets ICH and USP standards for most Class 2 and Class 3 solvents and half of Class 1 solvents.
Revolutionizing LC-MS with Next-Gen Separation for Cyclic Peptide Analysis
February 17th 2025Cyclic peptides, known for their stability and high specificity, are promising therapeutic agents in the fight against cancer, infections, and autoimmune diseases. However, developing effective cyclic peptides presents numerous challenges, including poor pharmacokinetics, efficacy, and toxicity. Traditional methods like liquid chromatography tandem-mass spectrometry (LC-MS/MS) often struggle with resolving isomeric linear peptide metabolites, posing significant risks in safety, efficacy, and regulatory approval. In this paper, Komal Kedia, PhD, will share how she leveraged MOBIE’s high-resolution ion mobility-mass spectrometry (IM-MS) system to achieve a 72% reduction in run times, 200% greater resolving power, and enhanced accuracy in identifying “soft spots” prone to enzymatic degradation.