Chromatographic Determination of the Association Constants Between Psoralen Derivatives and Modified β‐Cyclodextrin: Effect of Sucrose as a Co‐enhancer Association Agent

Abstract

The retention of psoralen derivatives, i.e., 8‐methoxypsoralen (8‐MOP), 5‐methoxypsoralen (5‐MOP), and trimethylpsoralen (TMP) in high performance liquid chromatography (HPLC) was investigated using a C₁₈ bond silica column, hydroxypropyl‐β‐cyclodextrin (HP‐β‐CD) as mobile phase additive (0–19 mM) and a wide range of column temperature (−5°C–55°C). Such a study was carried out to demonstrate the potential drug complexing role of this cyclodextrin for a future application in pharmaceutical formulation. Assuming a 1:1 stoichiometry, the association constants (K) were calculated from the chromatographic data. At a column temperature of −5°C, and in a 42% water–58% methanol (v/v) mixture, K was equal to 30, 75, and 40 M⁻¹ for the 8‐MOP/, 5MOP/, and TMP/, HP‐β‐CD associations, respectively. The thermodynamic parameters of the complexes were determined from linear van't Hoff plots for the three complexes. From the enthalpy and entropy changes, it appeared that the recognition mechanism of HP‐β‐CD for 8‐MOP and TMP was temperature dependent, and the hydrophobic effect between TMP and the flexible hydroxypropyl groups of HP‐β‐CD was counterbalanced by its steric hindrance. As well, the role of sucrose on this association was investigated. It was expected, that the sucrose would act on the psoralen derivatives/HP‐β‐CD association process by modifying the surface tension of the bulk solvent and increase the K _f values.

Keywords:

• HPLC
• Hydroxypropyl‐β‐cyclodextrin
• Psoralen
• Association‐constant
• Thermodynamic
• Sucrose