High‐Throughput Screening and Method Development Strategies to Separate Chiral Drug Compounds in HPLC, SFC, and CE

Supercritical fluid chromatography for the enantioseparation of pharmaceuticals

“…The effect is believed to last longer in apolar mobile phases (as is the case in SFC) than when polar eluents are used. A combined use of acidic and basic additives is claimed to reduce the memory effect in HPLC [17,100,101]. However, up till now there are no reports in the literature on the investigation of the memory effects in SFC.…”

“…This is a phenomenon where additives, after their removal from the mobile phase, leave a trace on the chiral selector of the CSP, altering its initial properties [17]. For HPLC this memory effect has been extensively studied and different rinsing procedures and additive uses were proposed [90][91][92][93][94][95].…”

“…While different approaches, such as asymmetric synthesis, enantioselective crystallisation and kinetic resolution procedures can be used to obtain pure enantiomers, chromatographic resolution remains the most favored and cost-effective approach, especially in early drug development [5,[13][14][15]. Chromatographic enantioseparations can be done with gas chromatography, thin layer chromatography, capillary electrophoresis, capillary electrochromatography, supercritical fluid chromatography and high-pressure liquid chromatography [16][17][18][19][20][21][22][23][24][25][26][27]. The easy applicability, plethora of reported applications, advanced instrumentation and extensive knowledge favored HPLC as most used separation technique in the pharmaceutical industry [14,[16][17][18]20,22,23,26,27].…”

“…Chromatographic enantioseparations can be done with gas chromatography, thin layer chromatography, capillary electrophoresis, capillary electrochromatography, supercritical fluid chromatography and high-pressure liquid chromatography [16][17][18][19][20][21][22][23][24][25][26][27]. The easy applicability, plethora of reported applications, advanced instrumentation and extensive knowledge favored HPLC as most used separation technique in the pharmaceutical industry [14,[16][17][18]20,22,23,26,27]. However, several limitations can be encountered during the development of chiral HPLC-methods, such as rather long equilibration-and analysis times and the need of using toxic and flammable solvents.…”

Emerging Analytical Separation Techniques with High Throughput Potential for Pharmaceutical Analysis, Part II: Novel Chromatographic Modes

“…The main difference between SFC and HPLC is the use of the supercritical fluid as MP, which usually consists of carbon dioxide with a modifier. Advantages of SFC over HPLC are that less organic solvent is required for the analysis because the main part of the MP is carbon dioxide, and that a faster analysis is obtained because higher flow rates can be applied [32][33][34]. The SFC separation mechanism is similar to NPLC or HILIC, i.e.…”