Investigation into the content and formation of trihalomethanes and molecular change of dissolved organic matter from a typical water plant in south China.

Trihalomethanes (THMs) are a class of disinfection by-products that were proved to have adverse effects to human health. Investigation into its content change and molecular composition variation of its main precursor, which is believed to be dissolved organic matter (DOM) during water purification process, can help understand the formation mechanism of THMs and optimize the processes in drinking water treatment plant (DWTP). This is of great significance to ensure the safety of urban water supply. In this study, detailed changes of THMs' content and formation potential were determined during the water purification process in summer and winter at a typical DWTP in south China. Specific molecular composition changes of DOM were also characterized by ultrahigh-resolution mass spectrometry, to comprehensively study its correlation with the formation of THMs in different water processing units and seasons. The result showed that chlorination will cause drastic changes of water quality and a sharp increase in the concentration of THMs (18.7 times in summer and 13.9 times in winter). Molecular-level characterization of DOM indicates that a range of lignin-like substance with lower O/C (< 0.5) and H/C (< 1.25) vanished and considerable amount of protein-like and tannins-like substance with higher H/C (> 1.25) and O/C (> 0.5) was formed after chlorination. Analysis of Cl-containing products demonstrated that a bulk of CHOCl1 and CHOCl2 compounds with moderate molecular weights were formed in both winter and summer. However, the newly formed CHOCl1 molecules showed a relatively higher mass weight in summer (> 500 Da) compared to winter (300-500 Da). Seasonal differences also emerged in the result of correlation between the trihalomethanes formation potential and total organic carbon. The correlation coefficient in summer (0.500) was lower than that in winter (0.843). The results suggested that the exhaustive reaction and contribution of DOM to THMs may vary in different seasons.

Development and validation of sensitive methods for simultaneous determination of 9 antiviral drugs in different various environmental matrices by UPLC-MS/MS.

Trace antiviral drug contamination in aquatic ecosystems is becoming a significant environmental concern that requires an urgent efficient determination method. Here we developed sensitive and robust multi-residue determination methods to simultaneously extract and analyze 9 commonly used antiviral drugs (abacavir, zidovudine, efavirenz, nevirapine, ritonavir, lopinavir, lamivudine, telbivudine and entecavir) in surface water, wastewater, sediment, and sludge. Water samples were extracted with solid-phase extraction (SPE) technique using tandem hydrophilic-lipophilic balance and graphitized carbon black cartridges, while sediment and sludge samples were extracted using QuEChERS (quick, easy, cheap, effective, rugged, and safe) method. The extraction conditions of SPE (pH and cartridge type) and QuEChERS (acetic acid content, salts reagent, and purification sorbent) methods were carefully optimized. We observed that under optimum conditions, the method quantification limits of the 9 antiviral drugs in water and solid samples ranged from 0.05 to 19.23 ng L-1 and from 0.02 to 7.38 ng g-1, respectively. For environmental samples spiking 3 different concentrations, the recovery values for the most targeted antiviral drugs ranged from 70 to 130%, except for efavirenz. All targeted antiviral drugs were detected in wastewater samples except for entecavir. We also found abacavir, efavirenz, ritonavir, lopinavir, and telbivudine in sediment and sludge samples. Notably, telbivudine was identified in all environmental matrices, with a high concentration of 127 ng L-1 and 222 ng g-1 in water and sediment samples, respectively.

Occurrence, removal and mass loads of antiviral drugs in seven wastewater treatment plants with various treatment processes.

Antiviral drugs are among the most common and important classes of pharmaceuticals to treat viral infections, however their continuous emission and persistence in the receiving environment has attracted increasing attention about their potential ecological risks. Here we investigated the occurrence, fate and mass load of 9 antiviral drugs for acquired immunodeficiency syndrome and hepatitis B, in 7 wastewater treatment plants (WWTPs) with different treatment processes in Guangdong, China. Totally, 8 target antiviral drugs were detected in the WWTPs influent wastewater, effluent wastewater and sludge, with maximal concentrations up to 7624 ng/L (telbivudine), 568 ng/L (telbivudine), and 2013 ng/g wet weight (telbivudine), respectively. The removal efficiency varied widely between different antiviral drugs, with the mean aqueous removal efficiency and total removal efficiency ranging from -6.2% (nevirapine) to 100% (lamivudine) and -1.2% (nevirapine) to 100% (lamivudine), respectively. Mass balance analysis showed that their elimination was mostly attributed to the biodegradation/biotransformation. The total back-estimated usage and emission of 9 target antiviral drugs were 77.8 t/y and 13.2 t/y in Guangdong province, China, respectively. Based on the sewage epidemiology approach, the consumption and emission of antiviral drugs in seven studied WWTPs were ranged at 2.31 mg/d/1000 people (nevirapine) to 4970 mg/d/1000 people (telbivudine), and 0 (lamivudine) to 900 mg/d/1000 people (telbivudine), respectively. Preliminary risk assessment showed that the antiviral drugs of zidovudine, ritonavir, lopinavir, and telbivudine in the receiving rivers could pose high ecological risks for aquatic environment. The findings from the present study illustrate the persistence of nevirapine in WWTPs, and provide essential evidence for further study into the development of wastewater treatment technologies.

Discovery of an Orally Active and Long-Acting DPP-IV Inhibitor through Property-Based Optimization with an in Silico Biotransformation Prediction Tool.

Long-acting dipeptidyl peptidase IV inhibitors have emerged as promising molecules for interventions for type 2 diabetes. Once weekly dosing brings greater patient compliance and more stable glycemic control. Starting from our previous highly potent compound with a thienoprimidine scaffold, which is unfortunately severely hit by hepatic biotransformation, a lead compound was rapidly generated by drawing on the experience of our previously discovered long-acting compounds with pyrrolopyrimidine scaffold. With the aid of an in silico biotransformation prediction tool, (R)-2-((2-(3-aminopiperidin-1-yl)-4-oxo-6-(pyridin-3-yl)thieno[3,2-d]pyrimidin-3(4H)-yl)methyl)-4-fluorobenzonitrile was eventually generated and determined to have high potency, a fine pharmacokinetic profile, and a long-acting in vivo efficacy.