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Determination of related substances of ceftaroline fosamil in a medicinal product.Identification of the degradation products by UPLC with diode array detection and tandem mass spectrometry.Fragmentation pattern of ceftaroline fosamil.Ceftaroline fosamil, the prodrug of ceftaroline, is an advanced-generation cephalosporin antibacterial agent approved for treatment in the European Union in 2012. The drug is dedicated to curing complicated skin and soft tissue infections and community-acquired pneumonia.The developed analytical method of high performance liquid chromatography (HPLC) followed by diode array detector (DAD) set at 243 nm was used to identify and determine degradation products of ceftaroline fosamil. The elaborated method demonstrated good selectivity and linearity [r > 0.998 for the range 0.8–1.2 mg/mL (80–120%) and r > 0.997 for the range 0.005–0.015 mg/mL (0.5–1.5%)]. Limit of detection (LOD) and limit of quantification (LOQ) values were equal to 0.15 μg/mL and 0.5 μg/mL, respectively. The forced decomposition of ceftaroline fosamil carried out under acidic, basic, oxidative, photolytic and thermal conditions revealed the high sensitivity of ceftaroline on photodegradation and thermolysis processes. Representative ceftaroline samples were selected and analysed by LC coupled with electrospray ionisation time-of-flight mass spectrometry (LC-ESI-Q-TOF-MS) to identify the related substances that appeared under stress conditions. The LC-DAD method was transferred without any modification to LC–MS/MS system, allowing it to correlate results back to the LC-DAD method. Eight unknown signals were detected in the photolytic and thermal stress solutions for ceftaroline fosamil.The evaluated method was applied to the analysis of a medicinal product containing ceftaroline fosamil − Zinforo™, 600 mg, powder for concentrate for solution for infusion.Moreover, the optimised conditions allowed for the successful separation of eight cephalosporin antibiotics possessing a molecular structure similar to ceftaroline (cefepime, cefapirin, ceftazidime, cefpirome, cefalonium, cefotaxime, cefquinome, cefalotin).