Hydrolysis is one of the most important abiotic processes leading to the degradation of organic compounds in aqueous media. Although there have been many reports concerning the biodegradability or photostability of the investigated compounds, much less information is available on their hydrolytic stability. Moreover, hydrolysis rates have been established using procedures other than the recommended standardized OECD 111 procedures. This standard ensures that 1st category reliability data for the ERA of pharmaceuticals is obtained. Therefore, in this study we have applied optimized analytical procedures utilizing HPLC for determination of degradation rates in aqueous environment of ciprofloxacin (CIP), norfloxacin (NOR), enrofloxacin (ENR) and metronidazole (MTZ). This study, aims to assess hydrolytic stabilities of these compounds, which are the four most commonly used pharmaceuticals. The developed procedures let us determine all of the analyzed pharmaceuticals in various pH values of solution, over three times magnitude linearity ranges, high precision (RSD % <8.2) as well as detection limits in the range of 0.007 to 0.033 mg L-1. Obtained analytical performance parameters enabled us to track in details hydrolytic kinetics even of the very low concentrations. The results clearly showed that the hydrolytic degradation of tested pharmaceuticals is below 10% in a pH range from 4 to 9. This means that the half-lives of these compounds in an aquatic environment are higher than 1 year at 25 °C. Thus, hydrolytic pathways do not lead to a fast degradation and reduced risk of persistency for the investigated compounds.