BrightSpec Blog

Molecular Rotational Resonance in Modern Pharmaceutical Analysis

Written by Christopher Thompson | Sep 12, 2024 5:07:07 PM

Modern analytical laboratories are shaped by a range of advanced instruments designed to probe, analyze, and provide critical data across several industries, including pharmaceutical. 

From chromatography and mass spectrometry (MS) to Fourier-transform infrared (FT-IR) and nuclear magnetic resonance (NMR) spectroscopy, these technologies have become integral to research, production, and quality control processes. They each have their limitations, particularly when it comes to overcoming certain analytical challenges. 

Enter Molecular Rotational Resonance (MRR) spectroscopy—a tested, yet newly revitalized technique that is transforming the way we approach complex analyses in the pharmaceutical industry.

MRR spectroscopy has been valued for its unique ability to deliver unambiguous structural information about compounds and isomers within mixtures, all without requiring pre-analysis separation. Historically, the technology was mostly confined to academic labs, where it was used to tackle particularly challenging compounds. Recent advancements in chirped pulse Fourier-transform microwave spectroscopy have breathed new life into MRR, making it more accessible and applicable to routine laboratory use. The commercialization of MRR has opened new avenues for its application, particularly in the pharmaceutical industry, where it holds great promise for accelerating drug development and refining analytical processes.

One of the most significant advantages of MRR is its ability to provide clear and definitive structural characterization of molecules, including isomers, within mixtures. Unlike NMR, which, while being the gold standard for structural identification, struggles with sensitivity in complex mixtures and requires expert interpretation, MRR can deliver precise 3D structural data quickly and without the need for separation. Furthermore, MRR offers a combination of the speed seen in MS with the detailed structural information characteristic of NMR, making it a powerful tool for high-throughput environments.

In the pharmaceutical sector, where the stakes are incredibly high—both in terms of financial investment and the need for accuracy—MRR could stand out as a valuable asset. The drug development process is notoriously risky and costly, with only about 12% of drugs entering clinical trials ultimately receiving FDA approval. Against this backdrop, MRR offers a way to streamline workflows, reduce the time needed for method development, and improve the efficiency of analysis, all of which are critical for bringing new drugs to market faster and more cost-effectively.

MRR’s utility is particularly evident in areas like residual solvent analysis, where it simplifies method development by eliminating the need for consumables and solvents, and in impurity characterization, where it can accurately distinguish between structurally similar molecules, including chiral impurities, without the need for chromatographic separation. This capability is invaluable in ensuring the quality and safety of pharmaceutical products, as even minor impurities can significantly impact the efficacy and safety of a drug.

Moreover, MRR’s role in direct online reaction monitoring presents a good opportunity for pharmaceutical manufacturers. By allowing for real-time monitoring of reaction mixtures without the need for off-line sampling or separation, MRR enhances process control and supports the goals of the Process Analytical Technology (PAT) initiative, which seeks to improve pharmaceutical manufacturing processes through real-time quality assurance.

As MRR technology continues to evolve and become more widely available, its potential applications in pharmaceutical analysis are likely to expand further. While traditional techniques will undoubtedly maintain their place in the analytical toolbox, the benefits of MRR—particularly in terms of speed, specificity, and the ability to handle complex mixtures—make it a compelling choice for laboratories looking to stay at the cutting edge of pharmaceutical research and development.

Read more about MRR in our recent article in Spectroscopy Online titled, “MRR: A New Tool in Applied Analysis for the Pharmaceutical Industry.