Identification and determination of ketotifen hydrogen fumarate, azelastine hydrochloride, dimetindene maleate and promethazine hydrochloride by densitometric method.

Conditions for determination of: ketotifen hydrogen fumarate, azelastine hydrochloride, dimetindene maleate and promethazine hydrochloride by densitometric method in substances and pharmaceuticals were provided. Maximum wavelenghts were: 228 nm for ketotifen hydrogen fumarate, 295 nm for azelastine hydrochloride, 265 nm for dimetindene maleate and 255 nm for promethazine hydrochloride. The limits of quantification were in the ranges of 0.2-5 microg/spot. The statistical data showed adequate accuracy and precision of developed methods.

Application of HILIC stationary phase to determination of dimethindene maleate in topical gel.

A novel high performance liquid chromatography method for the determination of dimethindene maleate in pharmaceutical gel using hydrophilic interaction liquid chromatography (HILIC) with UV detection was developed and validated. Following optimal conditions for the analysis of dimethindene maleate were used: analytical column SeQuant ZIC-HILIC (50mmx2.1mm, 5microm), and mobile phase consisted of a mixture of acetonitrile and aqueous solution of acetic acid (25mM) and ammonium acetate (2.5mM) (87.5:12.5, v:v). The analysis time was less than 3min at a flow rate of 0.3mlmin(-1). UV detection was performed at 258nm. The method was validated and system suitability parameters were evaluated. The method is suitable for application for routine determination of dimethindene maleate in topical pharmaceutical preparation.

Determination of dimethindene enantiomers in pharmaceuticals by capillary electrophoresis with carboxyethyl-beta-cyclodextrin.

Cyclodextrin-mediated capillary zone electrophoresis in a hydrodynamically closed separation system with suppressed electroosmotic flow and UV absorbance photometric detection was developed for a high effective separation and quantitation of dimethindene enantiomers in various pharmaceutical formulations (solution, gel, capsules). The running buffer consisted of epsilon-aminocaproic acid (20 mmol/l) adjusted to pH 4.5 with acetic acid, negatively charged carboxyethyl-beta-cyclodextrin (2.5 mg/ml), serving as chiral selector, and 0.1% (w/v) methylhydroxyethylcellulose, serving as an electroosmotic flow suppressor. The proposed method was successfully validated appraising parameters of sensitivity, linearity, precision, accuracy/recovery and robustness and it is useful for routine use.

Comparison of capillary zone electrophoresis and isotachophoresis determination of dimethindene enantiomers in pharmaceuticals using charged carboxyethyl-beta-cyclodextrin as a chiral selector.

Charged cyclodextrin-mediated capillary electrophoretic methods (capillary zone electrophoresis [CZE] and isotachophoresis [ITP]) in a hydrodynamically closed separation system with suppressed electroosmotic flow and UV absorbance photometric detection (for CZE) or conductivity detection (for ITP) were developed for a highly effective separation and quantitation of dimethindene enantiomers in various pharmaceutical formulations (solution, gel, capsules). Optimized electrolyte systems were based on low-mobility buffer constituents (epsilon-aminocaproic acid, beta-alanine, potassium acetate, acetic acid), negatively charged (at pH > 4.5) carboxyethyl-beta-cyclodextrin (CE-beta-CD), serving as chiral selector, and methylhydroxyethylcellulose, serving as an electroosmotic flow suppressor. Complete enantioseparations of dimethindene in the presence of low concentrations of CE-beta-CD (2.5 mg/ml in CZE, 6.0 mg/ml in ITP) clearly indicated a role of charge of this chiral selector in enantioresolution. It also outlined the potential of charged CD-derivatives as chiral selectors for various CE techniques. The proposed methods were successfully validated, appraising parameters of sensitivity, linearity, precision, accuracy/recovery, and robustness, and then, they were applied to pharmaceutical samples. Consistent results obtained by both CE methods indicate their usefulness for routine use.

[Dimethindene determination in various dosage forms by means of capillary isotachophoresis]. / Stanovenie dimetindenu v rôznych liekových formách kapilárnou izotachoforézou.

Capillary isotachophoresis was employed to determine dimethindene in various dosage forms. Several electrolyte systems of varying compositions and varying pH were tested. For validation of the method and the determination of dimethindene in real samples (gel, drops, capsules), two electrolyte systems were selected. Precision, correctness, linearity, robustness, and selectivity of the ITP method were evaluated for both electrolyte systems. The pre-treatment of the sample prior to analysis consisted in dissolving and diluting the pertinent dosage form containing dimethindene with demineralized water to the required concentration. The sample adjusted in this way was directly dosed into the apparatus.

Determination of dimethindene in human tears by high-performance liquid chromatography.

A high-performance liquid chromatographic method is described for the determination of dimethindene in human tears. The tear samples were diluted in a 0.01 M hydrochloric acid-n-propanol mixture to prevent the irreversible adsorption of dimethindene. The diluted samples were directly injected into the chromatographic system to avoid sample pretreatment. The validation data demonstrate that the method is specific, precise and accurate within the calibration range of 12 to 1000 ng/ml dimethindene free base.

[The effect of the hydrogen ion concentration on membrane transport of dissociated drugs from saturated solutions]. / Einfluss der Wasserstoffionenkonzentration auf den Membrantransport dissoziierender Arzneistoffe aus gesättigten Lösungen.

Dissociating drugs diffuse from saturated solutions with suspended drug particles across lipophilic membranes according to zero order kinetics. The highest rate is maintained even if large fractions of the drug are dissociated due to the pH-conditions of the solution. The pH range of the highest and pH-independent membrane transport corresponds with drug solubility/pH-profiles, showing the solubility of the undissociated drug.