Metformin and guanylurea in aquatic environments: an overview and improved analysis

Tao, Yunwen (2020) Metformin and guanylurea in aquatic environments: an overview and improved analysis. Masters thesis, Memorial University of Newfoundland.

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Abstract

Metformin, a biguanide in chemical classification, is widely used as one of the most effective first-line oral drugs for type 2 diabetes. It is difficult to be metabolized by the human body and exists in both urine and faeces samples. Guanylurea is metformin’s biotransformation product. Consequently, significant concentrations of metformin and guanylurea have been reported in wastewater treatment plants (WWTPs) and coastal aquatic environments. In this thesis, a comprehensive overview is conducted to discuss the occurrence, impact, analysis and treatment of metformin and guanylurea in coastal aquatic environments of Canada, USA and Europe. The maximum concentrations of metformin and guanylurea in surface water samples were as high as 59,000 and 4,502 ng L⁻¹, respectively. Metformin can be absorbed in non-target organisms by plants and in Atlantic salmon (Salmo salar). Guanylurea has a confirmed mitotic activity in plant cells. Analysis methods of metformin are currently developed based on high-performance liquid chromatography (HPLC) and gas chromatography–mass spectrometry (GC-MS). The removal of metformin from aquatic environments in the target regions is summarized. The review helps to fill a knowledge gap and provides insights for regulatory considerations. The potential options for managing these emerging pollutants are outlined too. To help better track the occurrence of the two non-volatile biguanide compounds in liquid samples, the improvement of existing GC-MS based methods for reliable metformin and guanylurea analysis is also conducted in this thesis. Derivatization of metformin and guanylurea is the key pre-treatment procedure before the associated GC-MS analysis. Four selected factors affecting for the derivatization were evaluated, and the optimal factors include temperature (90oC), reacting time (40 minutes), solvent (1,4-dioxane), and ratio (1.5:1) of reagent to target component. Buformin and N-methyl-bis(trifluoroacetamide) (MBTFA) were used as the internal standard (IS) and the derivatization reagent, respectively. Calibration curves were made based on the optimal conditions of derivatization for metformin and guanylurea with the R² values of calibration linearity achieved as 99.35% and 99.2%, respectively. The values of relative standard deviation (RSD%) of metformin and guanylurea based on seven repeated trails are 2.67% and 15.37%, respectively. The optimal conditions for enhancing the sensitization of metformin and guanylurea derivatization performance were obtained. The improved GC-MS analysis method was eventually applied for metformin and guanylurea analysis in real water samples. Detection of metformin and guanylurea in other types of real water samples could be conducted in the future like final effluents of wastewater treatment plants.

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