Compatibility of atenolol with excipients: LC-MS/TOF characterization of degradation/interaction products, and mechanisms of their formation.

A study was carried out to investigate compatibility of atenolol, a beta(1) blocker, with a variety of pharmaceutical excipients. The binary mixtures (1:1) of atenolol with the excipients were stored for 1 month at 40 degrees C/75% RH. The samples were directly observed for the physical changes, and also analyzed by a validated HPLC method to determine the chemical changes. The study revealed that atenolol was incompatible with ascorbic acid, citric acid and butylated hydroxyanisole. The degradation/interaction products formed in these mixtures were characterized by high resolution mass spectrometric and fragmentation analyses, using a LC-MS/TOF system. The identity of characterized structures was justified through mechanistic explanations.