Simultaneous quantification of commonly prescribed antiretroviral drugs and their selected metabolites in aqueous environmental samples by direct injection and solid phase extraction liquid chromatography - tandem mass spectrometry.

The widespread implementation of antiretroviral therapy medication has made antiretroviral drugs (ARVDs) a significant pharmaceutical class in regions of high HIV infection rates. However, relatively little is known regarding the environmental occurrence of these emerging contaminants, and this is especially true for their metabolites. In this work, we report analytical methods to study the simultaneous occurrence of a range of common ARVDs and some of their known metabolites in surface water and wastewater. A novel direct injection liquid chromatography-tandem mass spectrometry (LC-MS/MS) method is reported for the analysis of ARVDs of different therapeutic classes and their selected metabolites in wastewater samples. In addition, a solid phase extraction (SPE) procedure was developed for pre-concentration of ARVs and metabolites from surface water samples. The respective methods proved suitable for the quantitative analysis of six parent ARVDs from three ARV classes, as well as three metabolites. Method validation showed average recoveries of 86% for the direct injection method, and 64% for the SPE method. With the exception of Zidovudine and the metabolites of Zidovudine and Ritonavir, all target ARVDs were detected in wastewater samples from two wastewater treatment plants in the Western Cape, South Africa. Higher concentrations were generally measured in influent compared to effluent samples, in the dry compared to the wet season as well as in chlorinated compared to uv-irradiated effluents. This study contributes for the first time quantitative data on the environmental occurrence of the known metabolites of Nevirapine (12-hydroxy-Nevirapine) and Efavirenz (8,14-dihydroxy-Efavirenz).