As requested by regulatory authorities, impurity profiling is an important issue of quality control. In this work, a simple and sensitive liquid chromatographic (LC) method compatible with mass spectrometry (MS) was developed to study related substances and degradation products in sodium cromoglycate drug substance and eye drops. The method used a Sunfire column (4.6 mm × 150 mm, 3.5 μm). Mobile phase A consisted of 10 mM ammonium formate and mobile phase B was acetonitrile. Linear gradient elution with a post-run time of 8 min was performed as follows: 0–30 min, 3% B to 50% B; 30–35 min, 50% B. The flow rate was set at 1.0 mL/min. Degradation experiments were performed to check the stability indicating properties of the developed method. Based on MSn spectral data and exact mass measurements, the chemical structures of 2 unknown impurities and 6 unknown degradation products were characterized, including impurity C listed in the European Pharmacopoeia as unknown structure. In addition, a plausible mechanism for the formation of the degradation products was also proposed.