Competitive complexation and SPE techniques combined with liquid chromatography for the separation and determination of cyclodextrin encapsulated drug substances

A new onalytical procedure, combining sample pretreatment with solid phase extroction ond high performonce liquid chromatography, was developed and opplied to ketoprofen:cyclodextrin (CD) complexes. The significont differences in molar absorptivity between free and CD bound drugs leod to analytical errors up to 30%. Procedures routinely used to remove most of the common excipients proved to be inadequate, creating the necessity of more specific (HPLC) onalytical methods including the step of dissociotion ond separation of drugs from CDs before the quontitation by UV detector. In the case of complexes such as Ketoprofen: CDs, strong binding to CDs inhibits the dissociation. Prior to the anolysis, the addition of molecules competing the binding in the CD cavity fairly decreased the strength of the complexation. When molecules, competing the binding to CD such os 1-odomantanol, were added to the samples the results were improved. The extent of the selective binding and the drug displocement were monitored with 1H-NMR spectroscopy and it was revealed that only partial dissociation of the complexes was obtained. The combination of the sample pre-treatment with a solid phase extraction technique was proved to be inevitable for the dissociation of the complex. When analyzing supramolecules spectral changes, arising from intramolecular and/or intermolecular interactions, are expected. Cansequently, analytical methods utilized should be carefully revised.