Detecting Residual Solvents In API

Detection of Residual Solvents in a Large-Molecule API by 1H  NMR Spectroscopy

Authors: Charlotte A. Carroll, Andrew C. Kolbert, and Tom Feinberg

Summary: The determination of residual solvents in an API by headspace GC-MS often requires the performance of multiple analyses, particularly when the potential solvents are unknown. Issues with detection of less volatile or non-soluble solvents have also been encountered. Therefore, a limits test using 1D H NMR Nuclear Magnetic Resonance (NMR) Spectroscopy has been developed and qualified on a representative group of solvents. In this case, the solvents are chosen based on the synthetic and processing scheme of the large-molecule protein API (36kDA) and are a subset of the Class 2 and Class 3 solvents as listed in USP<467>.