Uptake and metabolism of clarithromycin and sulfadiazine in lettuce

Abstract

Antibiotics are introduced into agricultural fields by the application of manure or biosolids, or via irrigation using reclaimed wastewater. Antibiotics can enter the terrestrial food chains through plant uptake, which forms an alternative pathway for human exposure to antibiotics. However, previous studies mainly focused on detecting residues of the parent antibiotics, while ignoring the identification of antibiotics transformation products in plants. Here, we evaluated the uptake and metabolism of clarithromycin (CLA) and sulfadiazine (SDZ) in lettuce under controlled hydroponic conditions. The antibiotics and their metabolites were identified by ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-QToF-MS/MS) and ultra-performance liquid chromatograph Micromass triple quadrupole mass spectrometry (UPLC-QqQ-MS/MS). The structure of CLA, SDZ and N-acetylated SDZ were confirmed with synthesized standards, verifying the reliability of the identification method. Eight metabolites of CLA and two metabolites of SDZ were detected in both the leaves and roots of lettuce. The metabolites of CLA included phases I and II transformation products, while only phase II metabolites of SDZ were observed in lettuce. The proportion of CLA metabolites was estimated to be greater than 70%, indicating that most of the CLA was metabolized in plant tissues. The proportion of SDZ metabolites was lower than 12% in the leaves and 10% in the roots. Some metabolites might have the ability to increase or acquire antibacterial activity. Therefore, in addition to the parent compounds, metabolites of antibiotics in edible vegetables are also worthy of study for risk assessment and to determine the consequences of long-term exposure.

Keywords: Antibiotics; Clarithromycin; Lettuce; Plant metabolism; Sulfadiazine.