Sulfated Β-cyclodextrin Research Articles

A novel approach to supramolecular Aggregation-Induced emission using tetracationic tetraphenylethylene and sulfated β-Cyclodextrin

The combination of aggregation-induced emission-based luminogens (AIEgens) with supramolecular chemistry has gained significant attention due to its ability to produce intense emission even at low concentrations. In this study, we report a supramolecular arrangement characterized by aggregation-induced emission through the integration of tetracationic tetraphenylethylene with a macrocyclic polyanionic derivative of β-cyclodextrin. Despite the exploration of ionic derivatives of cyclodextrins in pharmaceutical and host–guest supramolecular chemistry, the phenomenon of supramolecular aggregation-induced emission based on non-covalent interactions between the ionic derivative of β-cyclodextrin and derivatives of tetraphenylethyelene, a class of AIEgens, has received limited investigation. Our work explores AIE shown by the allylimidazolium derivative of tetracationic tetraphenylethyelene (ALITPE) induced by complexation with polyanionic sulfated β-cyclodextrin (SCD). The effectiveness of the emission intensity of this supramolecular assembly based on AIE is confirmed by steady-state and time-resolved fluorescence measurements, which are supported by ground-state absorption measurements. We also investigate the effect of changes in external environment, such as temperature, pH, and ionic strength, on the supramolecular assembly. Moreover, the aggregation behavior of ALITPE with SCD is comparatively studied with neutral native β-cyclodextrin, highlighting the contribution of high negative charge density on the surface of SCD for efficient aggregation with ALITPE molecules. Additionally, Molecular Docking calculations are employed to provide insights into the aggregation behavior of ALITPE molecules induced by SCD. Overall, our findings demonstrate the potential applicability of the ALITPE/SCD supramolecular assembly as a potential fluorescent sensing probe for various biological applications.

Al3+-Responsive Ratiometric Fluorescent Sensor for Creatinine Detection: Thioflavin-T and Sulfated-β-Cyclodextrin Synergy.

Kidney disorders are a rising global health issue, necessitating early diagnosis for effective treatment. Creatinine, a metabolic waste product from muscles, serves as an ideal biomarker for kidney damage. The existing optical methods for creatinine detection often involve labor-intensive synthesis processes and present challenges with the aqueous solubility and sensitivity to experimental variations. In this study, we introduce a straightforward fluorescence "turn-on" ratiometric sensor system for creatinine detection in aqueous media with a limit of detection of 0.5 μM. The sensor is based on sulfated-β-cyclodextrin (SCD)-templated H-aggregate of a commercially available, ultrafast rotor dye thioflavin-T (ThT). The Al3+ ion-induced dissociation of ThT-SCD aggregates, followed by reassociation upon creatinine addition, generates a detectable signal. The modulation of monomer/aggregate equilibrium due to the disassembly/reassembly of the ThT-SCD system under Al3+/creatinine influence serves as the optimal strategy for ratiometric creatinine detection in aqueous media. Our sensor framework offers several advantages: utilization of the readily available dye ThT, which eliminates the need for a laborious synthesis of custom fluorescent probes; ratiometric sensing, which improves quantitative analysis accuracy; and compatibility with complex aqueous media. The sensor's practical utility has been successfully demonstrated in artificial urine samples. In summary, our sensor system represents a significant advancement in the rapid, selective, and sensitive detection of the clinically crucial bioanalyte creatinine, offering potential benefits for the early diagnosis and management of kidney disorders.

The separation of the enantiomers of diquats by capillary electrophoresis using randomly sulfated cyclodextrins as chiral selectors.

Diquats, derivatives of the widely used herbicide diquat, represent a new class of functional organic molecules. A combination of their special electrochemical properties and axial chirality could potentially result in their important applications in supramolecular chemistry, chiral catalysis, and chiral analysis. However, prior to their practical applications, the diquats have to be prepared in enantiomerically pure forms and the enantiomeric purity of their P- and M-isomers has to be checked. Hence, a chiral capillary electrophoresis (CE) method has been developed and applied for separation of P- and M-enantiomers of 11 new diquats. Fast and better than baseline CE separations of enantiomers of all 11 diquats within a short time 5-7min were achieved using acidic buffer, 22mM NaOH, 35mM H3 PO4 , pH 2.5, as a background electrolyte, and 6mM randomly sulfated α-, β-, and γ-cyclodextrins as chiral selectors. The most successful selector was sulfated γ-cyclodextrin, which baseline separated the enantiomers of all 11 diquats, followed by sulfated β-cyclodextrin and sulfated α-cyclodextrin, which baseline separated enantiomers of 10 and nine diquats, respectively. Using this method, a high enantiopurity degree of the isolated P- and M-enantiomers of three diquats with a defined absolute configuration was confirmed and their migration order was identified.

Investigation of the anticoagulant activity of cyclic sulfated glycosaminoglycan mimetics

Thrombotic disorders are among the leading causes of deaths worldwide. Anticoagulants are frequently prescribed for their prevention and/or treatment. Current anticoagulants, which target either thrombin or factor Xa, are plagued with a number of drawbacks, the most important of which is the increased risk of internal bleeding. To develop better antithrombotic agents, the anticoagulant activity of cyclic glycosaminoglycan mimetics was evaluated. Human plasma clotting assays and enzyme inhibition assays were exploited to evaluate the anticoagulant activity of sulfated β-cyclodextrin (SBCD) and its three analogs: sulfated α-cyclodextrin, β-cyclodextrin, and methylated β-cyclodextrin. In normal human plasma, SBCD selectively doubled the activated partial thromboplastin time (APTT) at ∼9 μg/mL, with no effect on prothrombin time (PT) at the same concentration. Likewise, SBCD doubled APTT at ∼9 μg/mL and at ∼8 μg/mL in antithrombin-deficient plasma and heparin cofactor II-deficient plasma, respectively. Interestingly, the three SBCD derivatives were inactive at the highest concentrations tested which highlighted the importance of the sulfate groups and the size of the molecule. Enzyme assays revealed that SBCD inhibits factor XIa (FXIa) with an IC50 value of ∼20 μg/mL and efficacy of near 100%. SBCD did not inhibit other related proteins including thrombin, factor IXa, factor Xa, factor XIIa, factor XIIIa, plasmin, chymotrypsin, or trypsin at the highest concentrations tested demonstrating a significant selectivity. In Michaelis-Menten kinetics, SBCD decreased the VMAX and increased the KM of FXIa hydrolysis of a tripeptide chromogenic substrate indicating a mixed inhibition mechanism. Together, it appears that SBCD is a potent and selective inhibitor of human FXIa with substantial anticoagulant activity in human plasma. Overall, this study introduces SBCD as a promising lead for further development as a safer anticoagulant.

Separation of tamsulosin enantiomers by capillary electrophoresis with tandem mass spectrometry and online stacking preconcentration.

The aim of our work was to develop a new method for the analysis of tamsulosin enantiomers by capillary electrophoresis connected with tandem mass spectrometry. The pharmacologically active (R)-enantiomer of tamsulosin, is used to treat benign prostatic hyperplasia and chronic prostatitis. Under the optimal conditions, background electrolyte consisting of 200 mM acetic acid titrated with NH4OH to pH 4.0 containing 4.0 mg mL-1 sulfated β-cyclodextrin, an injection time of 40 s at 50 mbar, a voltage of 20 kV and an optimized MS set-up (as e.g., sheath liquid containing 75 : 24.9 : 0.1 MeOH, H2O, and formic acid, v/v), a limit of detection of 1.6 nmol L-1 was achieved. The method was validated in terms of linearity, detection and quantification limits, precision, recovery, and selectivity. The results showed that the method can be used for the analysis of tamsulosin enantiomers in environmental samples, but generally, it can be applied to many different analytical tasks.

Cotton Fabrics Finished By Natural And Sulfated β-Cyclodextrin Inclusion Complexes Of Silver Nanoparticles For Biomedical Applications

In this study, it was aimed to compare the properties of cotton fabrics finished by natural and sulfated β-cyclodextrin complexes of silver nanoparticles (AgNPs) for biomedical applications. For this aim, sulfated β-cyclodextrin (S-β-CD) was obtained from β-CD and they were applied to cotton fabrics with and without EDTA crosslinking agent. Then, all the fabrics were treated with AgNPs and inclusion complexes were formed. Within the scope of the study, antibacterial activity, washing stability, add-on, tensile strength, handle and color change of the samples were tested and compared to each other. In addition, SEM and EDX were performed on the samples to characterize the effects of finishing, FT-IR analysis was performed to characterize the chemical structures of β-CD and S-β-CD powders and XRD analysis was performed to characterize the AgNPs. As a result of the study, the treatment of S-β-CD complex with AgNPs and crosslinking this complex to cotton sample by means of EDTA was found to be the most favorable method.

Guest Binding with Sulfated Cyclodextrins: Does the Size of Cavity Matter?

Sulfated cyclodextrins have recently emerged as potential candidates for producing host-induced guest aggregation with properties better than p-sulfonatocalixarenes that have previously shown numerous applications involving the phenomena of host-induced guest aggregation. In the class of sulfated cyclodextrins (SCD), sulfated β-cyclodextrin (β-SCD) remains the most extensively investigated host molecule. Although it is assumed that the host-induced guest aggregation is predominantly an outcome of interaction of the guest molecule with the charges on the exterior of SCD cavity, it has not been deciphered whether the variation in the cavity size will make a difference in the efficiency of host-induced guest-aggregation process. In this investigation, we present a systematic study of host-induced guest aggregation of a cationic molecular rotor dye, Thioflavin T (ThT) with three different sulfated cyclodextrin molecules, α-SCD, β-SCD and γ-SCD, which differ in their cavity size, using steady-state emission, ground-state absorption and time-resolved emission measurements. The obtained photophysical properties of ThT, upon interaction with different SCD molecules, indicate that the binding strength of ThT with different SCD molecules correlate with the cavity size of the host molecule, giving rise to the strongest complexation of ThT with the largest host molecule (γ-SCD). The binding affinity of ThT towards different host molecules has been supported by molecular docking calculations. The results obtained are further supported with the temperature and ionic strength dependent studies performed on the host-guest complex. Our results indicate that for host-induced guest aggregation, involving oppositely charged molecules, the size of the cavity also plays a crucial role beside the charge density on the exterior of host cavity.

Polyanionic Cyclodextrin-Induced Supramolecular Assembly of a Cationic Tetraphenylethylene Derivative with Aggregation-Induced Emission.

The combination of supramolecular chemistry and aggregation-induced emission-based luminogens (AIEgens) has recently attracted tremendous attention because of its ability to offer large emission enhancement even in substantially dilute solutions. In this work, a new aggregation-induced emission (AIE)-based supramolecular assembly has been reported, which consists of a polyanionic cyclodextrin derivative and a tetracationic tetraphenylethylene (TPE) derivative. Ionic cyclodextrins have attracted significant attention in host-guest supramolecular chemistry and pharmaceutical industry. However, ionic derivatives of β-cyclodextrins have not been explored to establish noncovalent interactions-based aggregation assembly of the most popular class of AIEgens, i.e., tetraphenylethylene derivatives. The current report demonstrates AIE of a tetracationic methyl pyridinium derivative of tetraphenylethylene (TPy-TPE) induced by a polyanionic sulfated β-cyclodextrin (S-βCD). The AIE-based supramolecular assembly has been thoroughly investigated using steady-state fluorescence, ground-state absorbance, and time-resolved fluorescence measurements. Further, the response of the supramolecular assembly towards external stimuli, such as, ionic strength, pH, and temperature, has been investigated. In addition, the complexation behavior of the TPE derivative has also been compared with the native neutral β-cyclodextrin derivative, which delineates the important role of the negatively charged portal of S-βCD in inducing aggregation of the TPy-TPE. The stoichiometry of the complex has been found to be 3:1 for TPy-TPE:S-βCD, using Job's plot analysis. Finally, to get insights into the underlying interactions between the supramolecular assembly components, molecular docking calculations have been performed.

A simple and cost-effective synthesis of sulfated β-cyclodextrin and its application as chiral mobile phase additive in the separation of cloperastine enantiomers

A simple and cost-effective method for the synthesis of sulfated β-cyclodextrin, one of the most widely used chiral mobile phase additives, using sulfamic acid as a sulfonating agent has been described. The method was optimized, and the synthesized product was characterized by spectroscopic, size-exclusion chromatographic, thermal, and microscopic methods and was compared to the marketed Sigma Aldrich sulfated β-cyclodextrin. β-Cyclodextrin, hydroxypropyl β-cyclodextrin, sulfated β-cyclodextrin (marketed and synthesized) were evaluated as chiral mobile phase additives for the enantiomeric separation of cloperastine, an antitussive agent, using reversed-phase HPLC. Under optimized conditions, a resolution of 3.14 was achieved within 15 min on an achiral Kromasil C8 (150 × 4.6 mm, 5 µm) column, with 5 mM monopotassium phosphate containing 10 mM synthesized sulfated β-cyclodextrin pH 3.0 and 45% methanol as mobile phase. The method utilizing synthesized sulfated β-cyclodextrin as chiral mobile phase additive was validated as per ICH guidelines and applied for the quantitative determination of cloperastine enantiomers in active pharmaceutical ingredients and pharmaceutical formulations. The selectivity changes imparted by sulfated β-cyclodextrin were proven to be beneficial for chiral separation. For the enantiomeric separation of cloperastine, synthesized sulfated β-cyclodextrin afforded better resolution than marketed sulfated β-cyclodextrin.

Sulfated-β-cyclodextrin templated aggregation of a metachromatic dye, Basic Orange 21: A photophysical investigation

ABSTRACT The recently discovered molecular rotor and supravital dye, Basic Orange-21 (BO21), has shown improved differential counting of leukocytes through metachromasia (change in colour), which is believed to be due to the aggregation of chromophores. Thus, investigation on the aggregation behaviour of BO21 holds special importance and may help us to delineate its spectroscopic behaviour. In this contribution, we have investigated the photophysical behaviour of BO21 in presence of a negatively charged supramolecular host, sulfated-β-cyclodextrin (SC), using ground-state absorption, steady-state and time-resolved emission spectroscopy including ultrafast fluorescence spectroscopy, and molecular docking calculations. The spectral characteristics of BO21 display extreme modulations in presence of SCD, with features similar to that observed for BO21 during its metachromatic behaviour. These spectroscopic features have been rationalised in terms of aggregation of BO21 molecules in the vicinity of SCD, which are also extremely sensitive to external stimuli, such as, ionic strength and temperature of the medium.

Binding Constants Determination of Ofloxacin and Ornidazole Enantiomers with Sulfated β-Cyclodextrin as Single Ligand by Capillary Electrophoresis using Three Different Linear Plotting Methods

The aim of this research is to use capillary electrophoresis to establish/determine the binding constants for ofloxacin and ornidazole enantiomers with the negatively charged chiral selector sulfated-β-cyclodextrin (S-β-CD). Using electrophoretic mobility values of ofloxacin and ornidazole enantiomers at various concentrations of S-β-CD used in the context of background electrolyte (BGE), binding constants were calculated using three separate linearization plots, namely double-reciprocal, X-reciprocal and Y-reciprocal. The R-ofloxacin enantiomer-S-β-CD complex had the highest inclusion affinity of the ofloxacin and ornidazole enantiomers, which matched with previously reported estimation. Every enantiomer-S-β-CD complex’s binding constants, as well as thermodynamic binding parameters, were calculated at different temperatures. The host-guest binding constants using double reciprocal fit showed greater linearity (R2 > 0.99) at all temperature ranges measured (15-30 ºC) as compared to the other two fit approaches. The thermodynamic complexation parameters were found to be dependent on the temperature of the enantiomers, as seen by the linear van’t Hoff (15-30 ºC) plot.

Electrostatic interactions between viologens and a sulfated β-cyclodextrin; formation of insoluble aggregates with benzyl viologens

Viologens are important compounds and are used in several applications. The interactions between viologens and a negatively charged cyclodextrin, sulfated β-cyclodextrin (sβ-CD), were studied using electrochemistry, 1H NMR and UV–Vis spectroscopy. Weak electrostatic interactions were found between the dicationic viologens (V2+) and the anionic cyclodextrin. The diffusion coefficient of ethyl viologen (EV2+) was reduced from 5.33 × 10−6 to 1.98 × 10−6 cm2 s−1 with an excess of sβ-CD. More significant electrostatic interactions were found between benzyl viologen (BV2+) and sβ-CD. The H atoms in the benzyl substituent, which appear as a singlet in the NMR experiment, were split into a multiplet in the presence of the sβ-CD, while the chemical shift of the H in the β position to the quaternary nitrogen, was shifted by 0.17 ppm in the presence of sβ-CD. Greater electrostatic interactions were evident between the benzyl radical cation (BV·+) and sβ-CD. Using cyclic voltammetry, reduction of the radical cation to the neutral benzyl viologen (BV0) was shifted by 230 mV to a lower potential, indicating that the reduction of the radical cation becomes considerably more difficult in the presence of sβ-CD. This was attributed to the formation of an insoluble BV·+:sβ-CD aggregate, which was also evident in rotating disc voltammetry, where the typical diffusion-limited currents were not observed and in spectroelectrochemistry experiments, where the deposition of the aggregate at the ITO electrode increased the absorbance of the radical species.

Quality by Design-Based Development of a Chiral Capillary Electrophoresis Method for the Determination of Dextrodropropizine and 1-Phenylpiperazine as Impurities of Levodropropizine

Based on a quality by design approach, a capillary electrophoresis method for the simultaneous determination of dextrodropropizine and the achiral precursor 1-phenylpiperazine in levodropropizine was developed. The analytical target profile was defined as a method allowing the simultaneous determination below the 0.5% level within a maximum analysis time of 20 min with an acceptable precision and accuracy. Based on scouting experiments, sulfated β-cyclodextrin in a 25 mM potassium phosphate buffer, pH 7.0, was selected. Subsequently, cyclodextrin concentration, propan-2-ol concentration, capillary temperature and applied voltage were identified as critical process parameters using a full factorial design followed by a central composite face-centered design for the final optimization of cyclodextrin concentration and temperature. The design space was obtained by Monte Carlo simulations. The final method comprised a 40/50.2 cm effective/total length, 75 µm inner diameter fused-silica-capillary, 25 mM potassium phosphate buffer, pH 7.0, containing 23.5 mg mL−1 sulfated β-cyclodextrin and 10% (v/v) propan-2-ol as background electrolyte, 16.3 °C capillary temperature and an applied voltage of 16.5 kV. The robustness was assessed using a Plackett–Burman design followed by method validation. Finally, the method was applied to the analysis levodropropizine reference substance of the European Pharmacopoeia and a liquid dosage form.

Stimulus-Responsive Supramolecular Host-Guest Assembly of a Cationic Pyrene Derivative with Sulfated β-Cyclodextrin.

In general, aggregation-prone organic molecules are prevented from self-aggregation in the presence of macrocyclic hosts like β-cyclodextrin because of their preference for the formation of inclusion complex with guest molecules. On the contrary, sulfate-laced β-cyclodextrin has been recently reported to induce the aggregation of some of the non-aggregation-prone organic dyes, which have been subsequently utilized for biosensing applications. In the present contribution, we report the interaction of a cationic organic probe molecule, 1-pyrene methyl amine (PMA), which belongs to one of the most useful families of organic fluorescent probes, that is, pyrene, with a sulfated β-cyclodextrin derivative (SCD). Interaction of a cationic probe with a β-cyclodextrin derivative was studied using a variety of photophysical methods such as ground-state absorption, steady-state emission, and time-resolved emission techniques. Detailed photophysical investigations have revealed that SCD induces the ground-state association of PMA molecules. This SCD-induced aggregation of PMA molecules has been attributed to the charge neutralization of the cationic probe by negatively charged sulfate groups, which subsequently lead to their association because of the close proximity on the rims of cyclodextrin. This monomer-dimer equilibrium of the PMA-SCD system is found to be extremely responsive to external chemical stimuli like temperature, pH, ionic strength of the medium, and organic solvent (dimethyl sulfoxide), which projects them as potential platforms for various sensing applications including bioanalytes. The supramolecular assembly has been demonstrated to sense arginine.

Determination of oxaliplatin enantiomers at attomolar levels by capillary electrophoresis connected with inductively coupled plasma mass spectrometry

The aim of this study was to develop a method for the separation of oxaliplatin enantiomers at attomolar concentration levels. A combination of capillary electrophoresis and inductively coupled plasma mass spectrometry was chosen due to their unique characteristics, including fast and easy modification of separation selectivity, and significant limits of detection and linearity. In the first step, we optimized conditions for the separation of oxaliplatin enantiomers including background electrolyte composition and concentration, pH, and type and concentration of the chiral selector. Under optimal conditions, sodium borate buffer pH 9.5, ionic strength 40 mmol L−1, with 60 mg mL−1 sulfated β-cyclodextrin, separation was obtained with a resolution of 2.0. This electrolyte system was then used in the ‘in-house’ connection of capillary electrophoresis with inductively coupled plasma mass spectrometer. In this instance, separation lasted for 9.5 min. Calibrations were linear in the range of 0.1–500 μg mL−1 with R2 of 0.9999. LOD and LOQ values were of 64 ng mL−1 and 116 ng mL−1 of oxaliplatin, respectively. This represents detection of 49 fg or 125 attomol of oxaliplatin enantiomers in the capillary electrophoresis injected sample zone. Finally, the method was successfully applied for detection of oxaliplatin enantiomers in spiked urine samples.

Sulfated β‐Cyclodextrin Templated Assembly and Disassembly of Acridine Orange: Unraveling Contrasting Binding Mechanisms and Light Off/On Switching

AbstractPresent article reports the intriguing aggregation‐deaggregation behavior of acridine orange (AOH+), as induced by the water soluble macrocyclic host, sulfated β‐cyclodextrin (SCD), and the results are compared with those obtained earlier in the presence of sulfobutylether‐β‐cyclodextrin (SBEβCD) host. While monomeric form of AOH+ is widely investigated, the aggregation behavior of AOH+ still remains to be quite less explored, though dye aggregation has a great consequence for its uses as a fluorescence probe for various biological and other microheterogeneous systems. It is observed that aggregation/dimerization of AOH+ is highly assisted by SCD at lower host concentration, resulting a drastic fluorescence quenching for AOH+. In contrast, at higher SCD concentrations the host drives the initially formed AOH+ aggregates/dimers to convert into the monomeric AOH+‐SCD exo and inclusion complexes, ensuing a huge enhancement for AOH+ fluorescence. Though similar host assisted sequential fluorescence turn‐off and turn‐on for AOH+ was also observed earlier on using SBEβCD host (Phys. Chem. Chem. Phys. 2017, 19, 24166), in the present case the effect is exceptionally very large, suggesting the SCD to be a very efficient host to induce such a fluorescence Off‐On switching for the cationic dye AOH+, as explored elaborately in the present study following various photochemical and other complementary measurements.

Fundamental aspects of field-amplified electrokinetic injection of cations for enantioselective capillary electrophoresis with sulfated cyclodextrins as selectors

Head-column field-amplified sample stacking of cations from a low conductivity sample followed by enantiomeric separation using negatively charged chiral selectors was studied experimentally and with computer simulation. Aspects investigated include the direct electrokinetic injection of the analytes into the background electrolyte, the use of a selector free buffer plug, the contribution of complexation within the buffer plug and the application of an additional water plug between sample and buffer plug. Attention was paid for changes of ionic strength which is known to have a significant impact on complexation and thus effective mobility. Racemic methadone was selected as a model compound, randomly substituted sulfated β-cyclodextrin as chiral selector and phosphate buffers (pH 6.3) for the background electrolyte and the buffer plug. Results confirm that the buffer plug is providing a spacer between cationic analytes and the negatively charged selector during electrokinetic injection. Simulation predicts the required length and composition of the plug for a given injection time to avoid an interference with the selector. A short water plug added between the low conductivity sample and a high conductivity buffer plug is demonstrated to provide best conditions to achieve high sensitivity in enantioselective drug assays with sulfated cyclodextrins as selectors.

Quality by design-assisted development of a capillary electrophoresis method for the chiral purity determination of dexmedetomidine.

Dexmedetomidine is a selective α2 -adrenergic agonist used for patient sedation, while its enantiomer levomedetomidine has no sedative effects. As CE has been shown to be a powerful technique for enantiomer analysis, the aim of the study was the quality by design-based development of a CE-based limit test for the enantiomeric impurity levomedetomidine. The analytical target profile was defined that the method should be able to determine levomedetomidine with acceptable precision and accuracy at the 0.1% level. From initial scouting experiments, sulfated β-cyclodextrin was selected as chiral selector. The critical process parameters were identified in a fractional factorial resolution V+ design, while a central composite face centered design and Monte Carlo simulations were used for defining the design space of the method. The selected working conditions were a 21.3/31.5 cm, 50 μm id fused-silica capillary, a 50 mM sodium phosphate buffer, pH 6.5, containing 40 mg/mL sulfated β-cyclodextrin, a capillary temperature of 17°C and an applied voltage of 10 kV. Validation according to the ICH guideline Q2(R1) demonstrated repeatability and intermediate precision of content and migration time between 9.3 and 4.2% with accuracy in the range of 92.0 and 98.9%.

Application of Guanidine Hcl to Improve Enantioseparation of a Model Basic Drug, Cetirizine, By Capillary Electrophoresis Using Sulfated Β-Cyclodextrin.

A common approach in resolving enantiomers of chiral basic drugs by capillary electrophoresis (CE) is to use cyclodextrins (especially their anionic derivatives) as chiral selector in the acidic buffer (pH ≤ 3) in normal or reversed (carrier) mode. Then, some organic modifiers are added to the buffer solution if the resolution is not satisfactory. In case of cetirizine (CTN), applying the same approach, i.e. a reversed mode capillary zone electrophoresis (CZE) method with an acidic buffer and sulfated-β-cyclodextrine (S-bCD) as chiral selector, was failed and no complete enantioseparation was achieved. Different organic modifiers, like urea and triethylamine HCl, were used to improve chiral resolution which led to partial resolution of the two peaks. Then, guanidine HCl at a concnetration of 100 mM was added to the running buffer and an acceptable resolution of the enantiomers of the drug was obtained. The method was successfully applied to determine optical purity of a levo-cetirizine (l-CTN) sample.

Diffusion in ternary aqueous {L-dopa + (NaSO3) -β-cyclodextrin} solutions using the pseudo-binary approximation

Mass transport in (drug + cyclodextrin) solutions is investigated by using Taylor dispersion technique, monitored by differential refractometry, to measure ternary mutual diffusion in aqueous solutions of {L-dopa + (NaSO3)n-β-CD} (the sodium salt of sulfated β-cyclodextrin). The values of the binary mutual diffusion coefficients of both aqueous L-dopa and aqueous (NaSO3)n-β-CD solutions are close to each other differing only by a few per cent units. As a result, the eigenvalues for the matrix of the ternary Dik diffusion coefficients for aqueous {L-dopa(1) + (NaSO3)n-β-CD(2)} solutions are nearly identical, and the numerical analysis of the Taylor dispersion data may be ill-conditioned in view of the unreliable data obtained from their analysis. To overcome these difficulties, the pseudo-binary diffusion approximation is used to evaluate in a simple way this ternary system. The pseudo-binary diffusion coefficient values found, Dp1 and Dp2, are very close to the binary diffusion ones, being the cross-coefficients approached zero, within the experimental error. From the obtained results, and under the circumstances of this study, we may deduct that no interaction between L-dopa and NaSO3ßCD was determined.