2.1.2. Process-Related Impurities

Small sharp peaks from process related impurities such as residual solvents and leachable were also identified and should be blinded out of HOS comparison as well [32,33]. For example, silicone oil used as a lubricant in DP containers could leach into the formulation and appear as a broad peak of polydimethylsiloxane (s) at 0.05 ppm, which can be further hydrolyzed to dimethylsilanediol and trimethylsilanol and appears as sharp peaks at 0.15 ppm (d) and 0.13 ppm (t), respectively (Figure 1A,C,D, right panels) [34]. Notably, the proton resonances of larger proteins could overlap with the spectral region around 0 ppm. Therefore, if NMR is used for the quantification of silicone oil components in protein formulations, T2-filtered CPMG pulse train may be used to remove protein resonances [35,36].
