Direct Analysis of Class 2 Residual Solvents Using Molecular Rotational Resonance Spectroscopy

Molecular 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.