Homogeneous Liquid–Liquid Microextraction

The development of liquid phase microextraction methods has led to significant progress in extraction processes by overcoming several challenges associated with conventional liquid–liquid extraction techniques. Liquid phase microextraction is a more cost-effective and eco-friendly alternative that is easier to implement compared to the traditional method. However, the use of water immiscible solvents as extractants in both liquid–liquid and dispersive liquid–liquid microextraction methods posed a challenge in extracting polar drugs. To address this limitation, homogeneous liquid–liquid microextraction emerged as the preferred mode for extracting polar analytes from complex matrices. HLLME uses hydrophilic, water-miscible solvents as extractants, leading to the formation of a homogeneous phase between the extractant and aqueous media. Because there is no interface between the sample and the extractant, HLLME provides superior extraction efficiency compared to other modes of liquid phase microextraction. Phase separation can be achieved by adding chemicals such as salt or sugar or manipulating the extractant's physicochemical properties, such as temperature or pH. In this chapter, we provide a detailed discussion of different homogeneous liquid–liquid microextraction modes, with emphasis on the fundamentals, the new developments and the applications.