Doctoral Degrees (Chemistry and Polymer Science)

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Browsing Doctoral Degrees (Chemistry and Polymer Science) by browse.metadata.advisor "de Villiers, André"

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    Novel analytical methods for the determination of antiretroviral drugs and their metabolites in environmental water samples.
    (Stellenbosch : Stellenbosch University, 2021-12) Mosekiemang, Tlou Thatayotlhe; de Villiers, André; Stander, Marietjie; Stellenbosch University. Faculty of Science. Dept. of Chemistry.
    ENGLISH SUMMARY: The occurrence and persistence of pharmaceuticals in aquatic environments is a topical public health issue because of their perpetual discharge into the environment as intact- or biotransformed products. The environmental effects for most these compounds are known, but much concern relates to the recently introduced pharmaceutical classes such as antiretroviral drugs (ARVDs), as well as their metabolites and transformation products. The potential presence of transformation products and metabolites of most ARVDs in wastewater samples is currently largely unknown. Most of the analytical methods developed to monitor ARVDs in aqueous environmental samples are targeted at selected compounds of a few therapeutic classes, warranting the need to expand their scope. ARVDs vary significantly in terms of molecular size, pKa and polarity, which further complicates the development of universal analytical methods for ARVD determination. The first task of this study was to develop a liquid chromatography-tandem mass spectrometric (LC-MS/MS) multiresidue method for the analysis of multiclass ARVDs and selected metabolites in wastewater samples. This necessitated the development of two separate sample preparation methods: one based on reversed phase (RP) solid phase extraction (SPE) sample clean-up and pre-concentration, and a second based on direct injection to correct for losses of polar ARVDs due to low breakthrough volumes on SPE. Application of the developed method to samples obtained from two wastewater treatment plants (WWTPs) in the Western Cape differing by advanced tertiary treatment processes allowed the first confirmation and quantification of two phase I ARVD metabolites, 8,14-dihydroxy efavirenz and 12-hydroxynevirapine. Furthermore, quantitative results confirm that levels of ARVDs in South African wastewaters are generally comparable to the rest of the world, and that they were mostly effectively removed by established treatment processes, with the exception of efavirenz and nevirapine. High concentrations were measured in the dry season, and the polar ARVDs were measured at high concentrations. WWTP treatment by uv-irradiation was found to be more effective at removing ARVDs compared to chlorination. In the second part of the study, supercritical fluid chromatography (SFC)-MS/MS was evaluated as an alternative to LC-MS/MS for the analysis of ARVDs in wastewater. Although the scope of the developed SFC-MS/MS method was more limited compared to LC, there was a high level of agreement in the quantitative data (recoveries, repeatability, and reproducibility) obtained by the two methods. These findings demonstrate for the first time the suitability of SFC-MS/MS for environmental analysis of ARVDs and their metabolites. Finally, a non-targeted LC-high resolution MS (HR-MS) method incorporating ion mobility spectrometry (IMS) was developed to screen for additional ARVDs and metabolites in wastewater samples. Based on IMS-filtered HR-MS low and high collision energy spectra and IMS collision cross section values, and using a suitable mass defect filter, several novel hydroxylated-, sulphated, carboxylated and glucuronidated metabolites for efavirenz, nevirapine, ritonavir and abacavir were identified for the first time in wastewater.