Synthesis and Characterization of 3-S-impurities in Timolol Maleate
Dejun Zhou, Keyang Wang, Yuying Zhang, Xiaoyue Liu, Xiaoxia MaoBackground:
Timolol maleate is clinically used for the treatment of hypertension, angina pectoris, tachycardia, and glaucoma.
Objective:
The aim of this study was to enhance the safe use of timolol maleate and investigate a synthesis method for 3-S-timolol, a newly identified impurity in timolol API (Active Pharmaceutical Ingredients).
Methods:
(S)-3-(tert-butylamino)propane-1,2-diol (1) was used as a raw material. 3-S-timolol maleate (7) was synthesized through a five-step reaction. Overall yield was 57.7%, with a purity of 98%.
Results:
The structure of the target compound was confirmed via analysis of its 1H nuclear magnetic resonance, 13C nuclear magnetic resonance, and high-resolution mass spectrometry spectra.
Conclusion:
The synthesis method was straightforward and yielded a high-purity product suitable for use as a reference in the analysis and identification of timolol maleate-related substances.