FOCUS ON : NMR spectroscopy, when limits matter
What is Nuclear Magnetic Resonance (NMR) Spectroscopy?
Imagine you have a radio that can “listen” to the tiny magnetic signals coming from atoms, such as hydrogen atoms in a compound. NMR spectroscopy is like that radio. It listens to how these atoms behave when placed in a strong magnetic field and hit with radio waves.
In NMR spectroscopy, every organic molecule produces a distinctive signal pattern, much like a fingerprint. Chemists act as molecular detectives, using these spectral fingerprints to determine both the presence and the amount of a substance, known as an analyte, within a sample.
NMR Spectroscopy is an essential tool in polymer chemistry, for monitoring the progression of polymerization reactions, providing detailed insights into the structure of molecules, the conversion and kinetics of polymerization reactions.
Modern NMR spectrometers support high-resolution measurements across various nuclei (e.g., 1H, 13C, 31P, 15N, and others) and enable advanced techniques such as relaxation time measurements and 2D-NMR. This technique is known for its high accuracy and reproducibility.
To ensure that these identifications and measurements are reliable, scientists use two important parameters: the Limit of Detection (LoD) and the Limit of Quantification (LoQ). The LoD refers to the smallest amount of analyte that can be confidently identified[1].
The Limit of Quantification (LoQ) is the lowest concentration of a compound that can be reliably measured with acceptable precision and accuracy. In NMR spectroscopy, having a low LoQ (which means better sensitivity) is crucial, especially when analyzing trace compounds.
Modern NMR instruments (like 400 MHz or higher) enhance sensitivity and peak separation, which helps lower the LoQ. However, achieving a low LoQ also depends on factors like signal-to-noise ratio (SNR), sample concentration, and acquisition settings.
Recently, at SEQENS, we have invested in a 500 MHz NMR equipment. To illustrate this concept, below is represented the different signals of LoQ/noise depending on the tested NMR instrument (250 MHz, 400MHz and 500MHz).
The importance of NMR spectroscopy for pharmaceutical-grade polymers manufacturing
When producing pharmaceutical-grade polymers, reaching a low LoQ enables the detection of trace impurities such as residual monomers, catalysts, or degradation products. This is key to meet strict regulatory standards set by agencies like the FDA and EMA, particularly those outlined in ICH guidelines.
In manufacturing, a low LoQ supports batch-to-batch consistency by enabling precise measurement of molecular features like copolymer ratios and end groups. It also plays a key role in characterizing functional groups that may be present in small amounts but are critical for the polymer’s function.
Additionally, NMR with a low LoQ is valuable for monitoring polymer stability, detecting early degradation, and ensuring proper drug loading and release in drug delivery systems. This level of sensitivity ensures that even low-concentration components are accurately quantified, supporting both performance and compliance.
At SEQENS, our 3 developments centers, Seqens’Lab, Porcheville, France; Aramon’Lab, Aramon, France and Boston’Lab, Devens, MA, USA are centralizing our expertise in Advanced Polymers and Lipids.
We cover manufacturing at different scales, purification & drying and characterization:
- Highly experienced dedicated R&D and Manufacturing teams are experts at synthesizing a broad range of polymetric materials lab scale, GMP pilots scale and industrial scales
- Purification and drying techniques: TFF, Chromatography, Spray-drying, Freeze-drying,
- Polymer and lipids characterization techniques for IPC & QC release: GPC/SEC, HPLC, NMR, FT-IR, NIR, DSC, TGA, CAD, MALS, DLS, Melt index, tap density
Our industrial expertise in polymers is backed by 25 years of production of GMP polymers for long-acting injectable forms, while we have more than 10 years of expertise in development of lipids for mRNA vaccine formulation.
Contact us to develop your tailored solution !
References
[1] Guide to NMR Method Development and Validation – Part I: Identification and Quantification; Eurolab, 2023. http://doi.org/10.13140/RG.2.2.30200.83208 (Accessed December 3, 2024)
