pH and temperature effects on the hydrolysis of three β-lactam antibiotics: ampicillin, cefalotin and cefoxitin.
An understanding of antibiotic hydrolysis rates is important for predicting their environmental persistence. Hydrolysis rates and Arrhenius constants were determined as a function of pH and temperature for three common β-lactam antibiotics, ampicillin, cefalotin, and cefoxitin. Antibiotic hydrolysis rates at pH4-9 at 25 °C, 50 °C, and 60 °C were quantified, and degradation products were identified. The three antibiotics hydrolyzed under ambient conditions (pH7 and 25 °C); half-lives ranged from 5.3 to 27 d. Base-catalyzed hydrolysis rates were significantly greater than acid-catalyzed and neutral pH hydrolysis rates. Hydrolysis rates increased 2.5- to 3.9-fold for a 10 °C increase in temperature. Based on the degradation product masses found, the likely functional groups that underwent hydrolysis were lactam, ester, carbamate, and amide moieties. Many of the proposed products resulting from the hydrolysis of ampicillin, cefalotin, and cefoxitin likely have reduced antimicrobial activity because many products contained a hydrated lactam ring. The results of this research demonstrate that β-lactam antibiotics hydrolyze under ambient pH and temperature conditions. Degradation of β-lactam antibiotics will likely occur over several weeks in most surface waters and over several days in more alkaline systems.
Department of Civil and Environmental Engineering, Washington State University, 405 Spokane Street, Pullman, WA 99164, USA.
Shannon M
SM
Mitchell
Jeffrey L
JL
Ullman
Amy L
AL
Teel
Richard J
RJ
Watts
D000667:Ampicillin / Q000737:chemistry / Q000378:metabolism*; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000378:metabolism*; D002440:Cefoxitin / Q000737:chemistry / Q000378:metabolism*; D002512:Cephalothin / Q000737:chemistry / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D013696:Temperature
D000900:Anti-Bacterial Agents; D002440:Cefoxitin; D000667:Ampicillin; D002512:Cephalothin
Ampicillin; Antibiotic hydrolysis; Cefalotin; Cefoxitin; Cephalosporin; β-lactam