Determination of the microscopic acid dissociation constant of piperacillin and identification of dissociated molecular forms

• Published in: Frontiers in chemistry 2023-04, Vol.11, p.1177128-1177128
• Main Authors: Li, Guoao, Wang, Yaling, Sun, Chengyi, Liu, Fei
• Format: Article
• Language: English
• Subjects: acid dissociation constant; Chemistry; molecular forms; piperacillin; potentiometric titration; β-lactam antibiotics
• ISSN: 2296-2646; 2296-2646
• DOI: 10.3389/fchem.2023.1177128

For amphoteric -lactam antibiotics, the acid dissociation constant (p ) is a fundamental parameter to characterize physicochemical and biochemical properties of antibiotics and to predict persistence and removal of drugs. p of piperacillin (PIP) is determined by potentiometric titration with a glass electrode. Electrospray ionization mass spectrometry (ESI-MS) is creatively applied to verify the reasonable p value at every dissociation step. Two microscopic p values (3.37 ± 0.06 and 8.96 ± 0.10) are identified and attributed to the direct dissociation of the carboxylic acid functional group and one secondary amide group, respectively. Different from other -lactam antibiotics, PIP presents a dissociation pattern where direct dissociation is involved instead of protonation dissociation. Moreover, the degradation tendency of PIP in an alkaline solution may alter the dissociation pattern or dismiss the corresponding p of the amphoteric -lactam antibiotics. This work offers a reliable determination of the acid dissociation constant of PIP and a clear interpretation of the effect of stability of antibiotics on the dissociation process.