NMR of PLGA

The most interesting tests we perform on biopolymers is that of identification, monomer ratio, and residual monomer by nuclear magnetic resonance (NMR) spectroscopy.  Exova operates a Bruker Avance III 500 MHz system under GMP quality assurance.

For a new polymer system, peak assignments in the NMR spectrum generally require a combination of ¹H, ¹³C spectra using DEPT-135, as well as 2D {¹H, ¹³C} HSQC spectra.  Exova has already determined peak assignments for lactide, glycolide, and caprolactone polymer systems of various copolymer ratios.

Once the peaks are unequivocally assigned, peak integrals can be used to calculate the monomer ratio from both the ¹H and ¹³C spectra.  While the ¹H spectrum is the most straight forward to obtain, we strongly advise clients to also use the ¹³C spectrum for confirmation.  However to obtain quantitative data from a ¹³C spectrum, one must use inverse-gated ¹H-decoupling and a long interpulse delay which requires much more time to acquire than a simple ¹H spectrum.

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The spectra also yield quantitative information about the residual monomer content.  The peak assignments for the example spectrum below have been confirmed by detailed analysis of the ¹H and ¹³C NMR spectra as explained above.  Note that Charts 2 and 3 are expansions of the Chart 1.

The peak assignments are as follows:

PLA CH - the polylactide methine proton quartet split by the PLA methyl protons (PLA CH₃),

PGY CH₂ - the polyglycolide methylene protons,

LAC CH - the lactide  monomer

GLY CH₂ - the methylene protons of the  glycolide monomer

HFIP is the solvent, deuterated hexafluoroisopropanol
 

While this example uses ¹H NMR to quantify these components, quantitative ¹³C NMR was also used to corroborate the ¹H results.

In our experience, NMR is preferable to gas chromatography for residual monomer.