## 4 Micellar Liquid Chromatography  
Micellar liquid chromatography (MLC) is a reversed-phase liquid chromatographic mode in which the stationary phase is nonpolar and the mobile phase is an aqueous solution of a surfactant at a concentration above the critical micellar concentration (CMC) [84]. In comparison with aqueous-organic mobile phases, the addition of a surfactant to the mobile phase in RP-HPLC modifies the chromatographic behavior, since it introduces a pseudo-stationary phase into which analytes can partition. In MLC, analyte retention depends on three phases: stationary phase, bulk solvent, and micellar pseudophase. Compounds are therefore separated based on their differential partitioning between these three phases. Most of the time, surfactants are added to the mobile phase to form micelles, but surfactant-coated stationary phases can also be used. For water-insoluble species, partitioning mainly occurs via direct transfer of analytes between the micellar pseudophase and the stationary phase [85]. Different papers with comprehensive overviews of MLC have been published [84; 85; 86; 87]. Micellar liquid chromatography has been investigated as an interesting approach for GAC, as it eliminates or reduces the use of organic solvents. Indeed, mobile phases contain aqueous solutions of a surfactant and a small percentage of organic modifier (mostly below 15%, \(v/v\)). Moreover, these micellar mobile phases are non-flammable, have a low toxicity, and do not produce hazardous waste because of the biodegradable character of the surfactants used [88]. For example, sodium dodecyl sulfate (SDS), the most commonly used surfactant in MLC, is a fatty alcohol sulfate that is aerobically degraded [89; 90; 91]. However, it is often necessary to add organic solvents to the aqueous solutions of micelles in order to improve MLC separations [86]. The most commonly used organic modifiers in MLC are propanol, butanol, and pentanol, which are less toxic than MeOH or ACN [4]. Another important advantage of MLC concerns sample treatment. In fact, the great solubilizing ability of micelles allows the direct injection of drugs in complex matrices (e.g., biological fluids and dosage forms) without the need for sample pretreatment other than filtration [84]. Moreover, MLC is compatible with existing RP-HPLC instruments. Thus, it does not require any modification of existing RP-HPLC instrumentation. Table 2 lists the different, recent applications of MLC for analysis of drugs in both pharmaceutical and biological matrices [92; 93; 94; 95; 96; 97; 98; 99; 100; 101; 102; 103; 104; 105; 106; 107; 108]. Although most of these methods used SDS as a surfactant, some of them also used Brij-35 [92; 93], cetyltrimethylammonium bromide (CTAB) [94], or Tween-20 [95]. In the majority of applications, hybrid micellar liquid chromatography was reported using mobile phases composed of an aqueous surfactant solution and a small volume of organic modifiers, such as n-propanol, n-butanol, and n-pentanol. As an example, [PERSON] [96] developed and validated a stability-indicating MLC method for the determination of three oxicans (piroxicam, tenoxicam, and lornoxicam) using a C8 column, and a mobile phase composed of 0.15 M SDS with 10% propanol. This method was applied to quality control of pharmaceutical preparations, including gel and suppositories, without pretreatment steps other than dilution and filtration. Another MLC method was established to quantify three selective serotonin reuptake inhibitors (citalopram, paroxetine, and fluoxetine) using a mobile phase buffered at pH 7, containing SDS and 6% (\(v/v\)) butanol [97]. The suitability of the method was then successfully checked through the analysis of tablets and biological samples (i.e., plasma and urine samples), without extraction steps from patients treated with selective serotonin reuptake inhibitors. There are also some interesting examples of green MLC analysis of pharmaceuticals using totally aqueous mobile phases [92; 93; 98; 99].