Far-UV CD is known for being prone to undesired spectral contributions from some buffers or excipients. But don't let this discourage you—with proper equipment, you can still get suitable results!
In this example from biosimilar development, one of the considered formulations contained histidine, which is commonly used to reduce aggregation propensity of monoclonal antibody products.
As histidine is chiral and highly absorbs, the formulation buffer showed a CD signal as high as the biosimilar sample! Is this an issue?
After averaging and baseline correction, spectra with a clear profile dominated by β-sheet contributions were obtained—just as expected for an antibody-based product.
This was possible by suitable sample preparation (buffer matching of all samples by dialysis against a common preparation of the formulation buffer), and using a Chirascan Q100 equipped with a flow cell of 0.1 mm path length, to maximise reproducibility and minimise the baseline contribution of the formulation buffer.