Packed Column Supercritical Fluid Chromatographic Determination of Acetaminophen, Propyphenazone, and Caffeine in Pharmaceutical Dosage Forms

Supercritical fluid chromatography (SFC), particularly with packed columns, has recently being gaining in popularity and is being investigated with increasing frequency for the characterization of pharmaceutical and biological agents. SFC can be described, roughly, as a form of high-performance liquid chromatography (HPLC), in which a fluid kept above its critical pressure and temperature, replaces the liquid-mixture mobile phase, which is normally used in HPLC. As the majority of drugs are either polar or moderately polar, pure supercritical carbon dioxide, being nonpolar, is not applicable to pharmaceutical analysis. This difficulty can be easily overcome by the use of a two-component mobile phase consisting of supercritical carbon dioxide and a small amount of a polar solvent. The increased solvent strength of this two-component mobile phase can be attributed to dipole-dipole, dipole-induced dipole, dispersive and hydrogen bonding (acidic and basic) forces. This mobile phase can solvate most known drugs and thus becomes a versatile mobile phase. The polar, organic solvent is known as the modifier, and modifiers used include methanol, ethanol, isopropanol, dichloromethane, tetrahydrofuran, dimethyl sulfoxide, and acetonitrile. The polar nature of this mobile phase can further be tailored to achieve retention by the addition of smaller quantities of weak acids or bases like trimethylamine, formic acid, acetic acid, and so on.