Roxithromycin

Macrolides are critical antibiotics featuring a macrocyclic lactone core with deoxy sugars. Understanding their gas‐phase fragmentation is challenging but essential for improving structural elucidation in mass spectrometry, which has implications for drug discovery and development.

We used electrospray ionization collision‐induced dissociation tandem mass spectrometry (ESI‐CID‐MS) combined with quantum chemical calculations to investigate the fragmentation pathways of erythromycin A and roxithromycin. This approach helps elucidate the preferred fragmentation routes influenced by protonation sites.

Macrolides showed similar fragmentation patterns, including sequential losses of saccharide or amino sugar units and dehydration from the macrocycle core. Multiple competitive pathways were observed, influenced by protonation sites. Computational studies confirmed the most favorable protonation sites and their impact on fragmentation, providing insights into key diagnostic product ions. Subsequent fragments involved rearrangement pathways such as alkene formation and cleavages via remote hydrogen transfers and pericyclic reactions.

Our integrated approach offers a comprehensive understanding of macrolide fragmentation, enhancing structural elucidation and potential applications in drug development. This study advances mass spectrometry analysis of macrolides, contributing to pharmaceutical research by integrating orthogonal annotation methods and fragmentation studies.

In recent years, due to large-scale production and widespread use, drugs have posed a potential threat to biological and human health and have received increasing attention. The occurrence and distribution of drugs in urban rivers are influenced by various factors, such as urbanization level, population density, regional geographical and climatic characteristics, and drug consumption habits. In October 2022, the Yongjiang River Basin was divided into four sub-basins： upstream, midstream, tributaries, and downstream. A total of 20 surface water and sediment samples were collected to explore the occurrence, spatial distribution, and ecological risks of drugs in water and sediment. Among the 40 target drugs, 22 drugs were detected in water samples, accounting for 55% of the target drugs, with a maximum concentration of 207.25 ng·L^-1, and 12 drugs were detected in sediment, accounting for 30% of the target drug, with a maximum concentration of 153.63 μg·kg^-1. The dominant species in water samples were metabolic drugs. In sediment, the dominant species in the upstream and midstream were quinolone antibiotics, while the dominant species in the tributaries and downstream were cardiovascular drugs. Nine drugs were detected in both water and sediment, with an apparent distribution coefficient K_d value of 5.0-385 029 L·kg^-1. According to the average lgK_oc value, the order from highest to lowest was： sertraline hydrochloride > ofloxacin > clarithromycin > D,L-venlafaxine > roxithromycin > sulfamethoxazole > fluoxetine > metoprolol > carbamazepine. Principal component analysis was used to analyze the source of drugs in water and four principal components explained 76.24% of the variation, corresponding to a source of medical wastewater, a mixed source of domestic wastewater and aquaculture wastewater, an untreated source of rural domestic wastewater, and an agricultural non-point source. Principal component analysis coupled multiple linear regression analysis well predicted the total concentration of drugs in 20 water samples （R² = 0.868）. Three drugs were present in the water sample that posed ecological risks, with risk quotients in the order of 1,7-dimethylxanthine > dehydrated erythromycin > carbamazepine, whereas only carbamazepine in sediment posed ecological risks. The cumulative risk quotient of multiple drugs in the water at 20 sampling sites was 1.22-16.27, all of which belonged to high risk, while the cumulative risk quotient of multiple drugs in sediment was 0.009~0.064, with no risk at site S11 and low risk at all other sites. The research results can be used to analyze the distribution mechanism of drugs between water and sediment, providing a technical basis for the prevention and control of drug pollution and environmental risks in urban rivers.