In this study, 100 mg/kg of amoxicillin (AMX) was added to pig manure during aerobic composting using a laboratory-scale reactor system, for better understanding the degradation of AMX and its potential risks. Qualitative and quantitative analysis of AMX and its main degradation products (DPs) were then conducted using solid phase extraction combined with high performance liquid chromatography-tandem mass spectrometry. Additionally, hydrolysis testing was performed to monitor DPs produced from AMX degradation under various controlled conditions. The results showed that AMX was unstable in compost and rapidly degraded into AMX penicilloic acid, AMX penilloic acid and AMX diketopiperazine, which all eventually degraded, leaving a structurally simple and stable end product, 3-(4-hydroxyphenyl) pyrazin-2-ol, which appeared to be nonallergenic and less toxic than DPs generated earlier in the composting process. Besides, AMX was more unstable and more apt to generate multiple DPs in alkaline conditions than in acidic or neutral conditions or in ultrapure water, while pH exerted a larger effect on AMX degradation than did divalent metal ions (Cu2+ and Zn2+). This study provides technical and methodological support to better achieve AMX residual treatment and to evaluate the safety of AMX DPs produced in huge quantities in compost in China. (C) 2017 Elsevier B.V. All rights reserved.