Capillary zone electrophoresis study of cyclodextrin – lipoic acid host‐guest interaction

Abstract

Lipoic acid is a naturally occurring compound which is being widely investigated for its therapeutic effects in the treatment or prevention of a variety of diseases associated with oxidative injury, particularly diabetes. The diversity of therapeutic applications of lipoic acid requires an appropriate formulation to control its bioavailability, site-targeting delivery and to overcome its inherent chemical instability. In this regard, cyclodextrins (CDs) are ideally suitable due to their well-documented ability to include in their cavity proper guest molecules and protect them from physical or chemical damages. Lipoic acid forms 1:1 inclusion complexes with betaCD as shown in a previous report of an extended investigation that also indicated the suitability of capillary zone electrophoresis (CZE) for the study of such host-guest interactions. In view of these possible applications, we extended the CZE analysis to determine the strength of binding, in a pH 9 phosphate buffer, of lipoic acid with other CD derivatives such as alphaCD, gammaCD and the alkylated derivatives of betaCD, namely (2-hydroxypropyl)-beta-CD (HPbetaCD), and heptakis(2,3,6-tri-O-methyl)-beta-CD (TMbetaCD). Once established that the easily available betaCD is the most suitable receptor for lipoic acid, we set up and here describe a simple and reliable procedure for the quantitative determination of lipoic acid in commercial dietary supplement tablets containing also other active substances and excipients.

Signal enhancement of carboxylic acids by inclusion with β‐cyclodextrin in negative high‐voltage‐assisted laser desorption ionization mass spectrometry

“…The latter results again suggest that the formation of β‐CD complexes is mainly due to specific interactions which may vary with the carboxylic acids. Moreover, the stability order of the different β‐CD complexes is LA > Phe > Val, which is in agreement with that reported previously …”

“…Clearly, pH 9 is a suitable pH condition for generating negative ions of the complex. Figure (d) shows that the optimal signal intensity of the complex is obtained when β‐CD and LA are equimolar, which is consistent with the formation of a 1:1 inclusion complex between β‐CD and LA in aqueous solution . The signal intensity of the complex declines when the concentration of β‐CD is higher than that of LA, because excess β‐CD in the solution may result in the formation of many nonspecific complexes during the ionization process, such as [2β‐CD + LA – 2H] 2– which competes with the formation of the specific 1:1 complex [β‐CD + LA – H] – ( vide infra ).…”

“…We have selected different carboxylic acids including aliphatic, aromatic and heteroatom‐containing compounds to investigate the effect of adding β‐CD on their negative HALDI‐MS signals. All these compounds can form 1:1 inclusion complexes with β‐CD in solution according to the previous reports …”

“…All these compounds can form 1:1 inclusion complexes with β-CD in solution according to the previous reports. [36][37][38][39][40][41][42] Figure 1 Rapid Commun. Mass Spectrom.…”

“…Figure 2(d) shows that the optimal signal intensity of the complex is obtained when β-CD and LA are equimolar, which is consistent with the formation of a 1:1 inclusion complex between β-CD and LA in aqueous solution. [36] The signal intensity of the complex declines when the concentration of β-CD is higher than that of LA, because excess β-CD in the solution may result in the formation of many nonspecific complexes during the ionization process, such as [2β-CD + LA -2H] 2which competes with the formation of the specific 1:1 complex [β-CD + LA -H] -(vide infra). Thus the optimal conditions of negative HALDI-MS for generating the complexes from the standard solutions are as follows: target HV À5.5 kV, laser energy 2.2 mJ/pulse, pH 9, and the concentration ratio of β-CD to carboxylic acid 1:1.…”