Current sample preparation methods for NTA of water are designed to concentrate as wide an array of sample components as possible into a single solution for injection. These have employed mostly single SPE , multi-layer SPE , or evaporative concentration . Despite this obvious logic, extraction of such a wide array of compound chemistries for instrumental analysis can present new or exacerbate analytical problems which affect performance and reliability including but not limited to: (a) insufficient chromatographic resolution which can in turn affect separation accuracy and precision when using retention time (tR) as a metric for compound identification, especially in liquid chromatography (LC); (b) increased droplet surface ion competition in electrospray ionisation (ESI) reducing or causing variable detector sensitivity and noise; and (c) much increased spectral complexity, which in turn increases the chances of incorrect spectral interpretation due to interferences in MS and MS/MS. Therefore, opting for some selectivity in the extraction step based on relatively simple, but still broad-reaching commonality in chemical properties for molecules present in water may improve the value and confidence in the overall NTA approach. The obvious disadvantage of such an approach is an increased workload with multiple different extraction modes required for chemicals with different properties being targeted. However, recognising that scientific knowledge of drinking water composition remains partial, and that even wide-scope extraction methods are highly unlikely to cover the entire chemical space anyway, multiple orthogonal and complementary methods are likely more effective at reducing this uncertainty and are ultimately more practical, reliable and arguably easier to automate as a result. The focus of this work lies in anionic components in drinking water as many such substances have recently emerged as very toxic in humans including a large array of perfluoroalkyl acids (PFAA) and disinfectant by-products (DBPs), such as haloacetic acids or oxyhalides, to name just a few. Sample preparation methods employing separate modes selective for acidic or basic analytes have been adopted for the analysis of persistent and mobile organic contaminants (PMOCs) for example , employing mixed-mode ion exchangers which are co-polymerised with an organic polymer backbone conferring wider extraction selectivity. Silica-based SAX resins have not been used in this field to date, due to the ionic strength required to remove strong acids effectively, but also finding such solutions that are compatible with chromatography and/or mass spectrometry detection.