Abstract Design of experiments (DoE) techniques have been widely used for various experimental measurements to optimize analytical methods with lower cost, reduced number of experiments, and increased efficiency. The current study intends to critically review the application of DoE in the development and optimization of dispersive liquid–liquid microextraction (DLLME) techniques for the analysis of organic pollutants in environmental samples using ultra–high performance liquid chromatography quadrupole time–of–flight mass spectrometry (UHPLC–QTOF–MS). The open literature has shown that the application of DoE is limited when it comes to the screening and optimization of DLLME factors. Full factorial design (FD), Box–Behnken design (BBD), and central composite design (CCD) were the most used among the various types of designs. According to data from the cited literature, the coupling technique was only applicable in the analysis of a few organic pollutants, which were mostly determined in surface water using the conventional DLLME technique. Additionally, illustrative examples with performance parameters demonstrating the advantages of DLLME with UHPLC–QTOF–MS optimized via DOE compared to one–factor–at–a–time (OFAT) approaches are briefly discussed. This review article also provides an overview of matrix effects (MEs) and discusses how using DoE can affect MEs during LC–MS analysis. A review of the literature indicates that applying DoE significantly enhances experimental efficiency, improves method performance, and aligns with green chemistry principles.
Makwakwa et al. (Thu,) studied this question.