Detecting possible modifications of therapeutic proteins is a critical element of the quality control of protein drugs. Typically, a number of techniques are used to evaluate different modifications of therapeutic protein formulations. Using heteronuclear NMR spectroscopy, we show that the difference between various insulin formulations can be detected "as is" with little pretreatment and quickly. As an application to the quality control of insulin formulations, the NMR approach was compared with four different analytical methods: with reverse phase high pressure liquid chromatography (HPLC) (for mutations), with size exclusion chromatography (for oligomerization), with electrophoresis (for denaturation), and with mass spectrometry (for deamidation). All of the results showed that this single NMR method can provide the specific signatures for each modification and information that is at least equivalent to that offered by the conventional analytical methods. Importantly, NMR could yield information at each amino acid residue level which no other technique provided. The suggested NMR method, then, can be considered to be a facile and effective means of evaluating therapeutic protein formulations in a multifaceted way.