Proposal for USP Chapter <320>: NMR-Based Determination of Degree of Hydrolysis and Monomer Ratio in Polyvinyl Alcohols

In the Pharmacopeial Forum, PF 51(3), a proposal for a new USP General Chapter <320> NMR Spectroscopy for the Determination of Degree of Hydrolysis for Polyvinyl Alcohol and Vinyl Alcohol Homopolymer, and Monomer Ratio for Vinyl Alcohol and Vinyl Acetate Copolymer has been published for public comment.

The draft, developed by the Excipients Test Methods Expert Committee (ETM EC), presents a validated analytical procedure using nuclear magnetic resonance (¹H-NMR) spectroscopy. The chapter is applicable for the determination of the degree of hydrolysis in polyvinyl alcohol and vinyl alcohol homopolymer and of the monomer ratio in vinyl alcohol vinyl acetate copolymer.

It is designed to support excipient users and manufacturers in more accurately characterizing the composition and variability of these widely used polymers. In the briefing notes, it is highlighted that compared to the existing official monograph method, which relies on classical titration and the use of methanol, the NMR-based procedure is more specific, less labor-intensive, and environmentally friendlier.

The method has been successfully validated and is suitable for the following materials:

• Polyvinyl Alcohol (degree of hydrolysis is 85%–89%)
• Vinyl Alcohol Homopolymer (degree of hydrolysis is NLT 90%)
• Vinyl Alcohol and Vinyl Acetate Copolymer (degree of hydrolysis is 70%–84%)

The chapter outlines detailed sample preparation steps and system suitability criteria, and provides equations for calculating both the degree of hydrolysis and the monomer ratio based on integrated NMR signals.

The new method will not replace the existing procedure available in the currently official monograph for Polyvinyl Alcohol. However, it offers an optional advanced analytical tool and supports USP’s broader efforts to modernize excipient testing standards.

The new draft can be viewed on the Pharmacopeial Forum website. Stakeholders are invited to review and comment on the draft chapter until 31 July 2025.