Study of the stability of 26 cytostatic drugs and metabolites in wastewater under different conditions

摘要

The stability of 26 cytostatic drugs (21 parent compounds and 5 metabolites) in wastewater was studied using liquid chromatography-electrospray-tandem mass spectrometry (LC-ESI-MS/MS). Wastewater aliquots were spiked with the target compounds at 1000 μg L~(-1) and stored in the dark under different temperature ( - 20, 4 and 25 ℃) and pH (acid and neutral) conditions for different periods of time (up to 3 months). The influence of these factors (temperature, pH and time) on the stability of the compounds was evaluated through an experimental design. The most negative factor was the time of storage, but temperature also exerted a very important influence. Acidification of the samples is a good option for some cytostatics (e.g., temozolomide, tamoxifen and its metabolites, and chlorambucil) but it may have a negative effect on others (e.g. ifosfamide). The design also showed correlations between factors indicating that an increase of the storage time is more relevant at high temperatures, while an increase of the temperature is more detrimental in non-acidified samples. After 3 months at - 20 ℃, all compounds with the exception of temozolomide, vinorelbine, imatinib and erlotinib presented recoveries below 80%. The most unstable compounds were oxaliplatin, 5-(3-N-methyltriazen-1-yl)-imidazole-4-carboxamide and chlorambucil. To the authors' knowledge, the stability data reported in the present study is the first ever published for most of the target compounds in wastewater. The results obtained point out storage at - 20 ℃ from collection to analysis as the best storage option.