Degradation and by-products identification of benzothiazoles and benzotriazoles during chlorination by LC-HR-MS/MS

Nowadays, chlorination is the most prevalent disinfection method applied for water treatment in Europe. Chlorine can be supplied as sodium hypochlorite (NaOCl) which reacts in water to produce the disinfectants hypochlorous acid (HOCl) and hypochlorite ion (OCl-), otherwise known as free chlorine. Although the primary purpose of chlorination is the elimination of micropollutants via oxidation, several investigations have shown that chlorine reacts with micropollutants leading in the production of undesired by-products. 1,3-benzothiazoles (BTHs) and 1,2,3-benzotriazoles (BTRs) are classified as high production volume emerging environmental pollutants due to their broad industrial and domestic application, and even though recently several analytical methods have been applied for their determination , there is still a lack of research for their by-products’ identification. Initially, the degradation of three BTHs (BTH, 2-OH-BTH and 2-amino-BTH) and four BTRs (1-H-BTRi, TTRi, XTRi and 1-OH-BTRi) during chlorination was investigated by UHPLC-MS/MS (QqQ). Although chlorination appeared to be an insufficient degradation process for BTH and 1-H-BTRi, all their examined substituted derivatives seem to be significantly degraded when the molar ratio of sodium hypochlorite and the target analytes was between 5000:1 – 1000:1. Then, LC high resolution MS/MS (q-TOFMS) was used to investigate the formation of by-products in the chlorinated samples. Two suspect by-products of 2-amino-BTH and one of XTRi were tentatively identified based on their probable structure, mass accuracy, retention time and fragmentation and isotopic pattern. An interesting observation was the formation of 1-H-BTRi as a degradation product of 1-OH-BTRi during chlorination. Moreover, post-acquisition non-target treatment of the MS data revealed several unknown by-products of the tested analytes

Malignancy Grade-Dependent Mapping of Metabolic Landscapes in Human Urothelial Bladder Cancer: Identification of Novel, Diagnostic, and Druggable Biomarkers

Background: Urothelial bladder cancer (UBC) is one of the cancers with the highest mortality rate and prevalence worldwide; however, the clinical management of the disease remains challenging. Metabolomics has emerged as a powerful tool with beneficial applications in cancer biology and thus can provide new insights on the underlying mechanisms of UBC progression and/or reveal novel diagnostic and therapeutic schemes. Methods: A collection of four human UBC cell lines that critically reflect the different malignancy grades of UBC was employed; RT4 (grade I), RT112 (grade II), T24 (grade III), and TCCSUP (grade IV). They were examined using Nuclear Magnetic Resonance, Mass Spectrometry, and advanced statistical approaches, with the goal of creating new metabolic profiles that are mechanistically associated with UBC progression toward metastasis. Results: Distinct metabolic profiles were observed for each cell line group, with T24 (grade III) cells exhibiting the most abundant metabolite contents. AMP and creatine phosphate were highly increased in the T24 cell line compared to the RT4 (grade I) cell line, indicating the major energetic transformation to which UBC cells are being subjected during metastasis. Thymosin β4 and β10 were also profiled with grade-specific patterns of expression, strongly suggesting the importance of actin-cytoskeleton dynamics for UBC advancement to metastatic and drug-tolerant forms. Conclusions: The present study unveils a novel and putatively druggable metabolic signature that holds strong promise for early diagnosis and the successful chemotherapy of UBC disease