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.
Kumar
Vijay
V
Department of Pharmaceutical Analysis, National Institute of Pharmaceutical Education and Research (NIPER), Punjab, India.
Shah
Ravi P
RP
Malik
Satish
S
Singh
Saranjit
S
D000319:Adrenergic beta-Antagonists / Q000737:chemistry*; D001205:Ascorbic Acid / Q000737:chemistry; D001262:Atenolol / Q000737:chemistry*; D002083:Butylated Hydroxyanisole; D002851:Chromatography, High Pressure Liquid; D019343:Citric Acid / Q000737:chemistry; D004344:Drug Incompatibility; D005079:Excipients / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D007202:Indicators and Reagents; D013058:Mass Spectrometry; D010592:Pharmaceutic Aids; D013056:Spectrophotometry, Ultraviolet
D000319:Adrenergic beta-Antagonists; D005079:Excipients; D007202:Indicators and Reagents; D010592:Pharmaceutic Aids; D002083:Butylated Hydroxyanisole; D019343:Citric Acid; D001262:Atenolol; D001205:Ascorbic Acid