Aleksandra Chmielewska

The research into the separation of drug enantiomers is closely related to the safety and efficiency of the drugs. The aim of this study was to develop a simple and validated HPLC method to analyze cetirizine enantiomers. In the case of liquid dosage forms, besides the active substance in large amounts there are usually also inactive ingredients such as methyl- and propylparaben. Unfortunately, these compounds can interfere with the analyte, inter alia during chiral separation of the analyte enantiomers. The proposed innovative two-step liquid-liquid extraction procedure allowed for the determination of cetirizine enantiomers (along with M and P parabens) also in liquid dosage forms. The main focus of this study was the chromatographic activity of cetirizine dihydrochloride on the proteinate-based chiral stationary phase. The chromatographic separation of cetirizine enantiomers was performed on an immobilized human serum albumin (HSA) column for the first time. Measurements were performed at a wavelength of 227 nm. Under optimal conditions, baseline separation of two enantiomers was obtained with 1.43 enantioseparation factor (α) and 1.82 resolution (R_s). Finally, the proposed method was successfully applied to the selected pharmaceutical formulations.

Generally, they are two systems expressing the amounts of active substance in a given drug product, i.e. mass and molar dose. Currently, the dose system based on the mass is widely used in which doses are expressed in grams or milligrams. On the other hand, the molar dose system is in direct relation to the number of molecules. Hence, the objective of this work was to compare both systems in order to find their advantages and disadvantages. Active substances belonging to the groups of antibiotics, nootropic agents, β-blockers, vitamins, GABA-analog, COX-2 inhibitors, calcium channel antagonists, benzodiazepine receptor agonists, lipid-modifying agents (fibrates), non-steroidal anti-inflammatory drugs (profens), estrogens, neuroleptics, analgesics and benzodiazepines were considered. Moreover, products containing two active substances were also taken into account. These are mixtures of hydrochlorothiazide with active substances influencing the renin-angiotensin system and combined oral contraceptives. For each active substance, belonging to the groups mentioned above molar doses were calculated from mass doses and molar mass. Hence, groups of drugs with a single active substance, drugs with similar pharmacological activities, pharmaceutical alternatives, and drugs with a single active ingredient manufactured in different doses were compared in order to find which dose system describes more adequately differences between and within the groups mentioned above. Comparisons were supported by a number of equations, which theoretically justify the data, and relationships derived from calculations.

A reversed‐phase high‐performance liquid chromatographic method with electrochemical detection for the quantitative determination of diclofenac potassium in plasma was developed. Naproxen was used as the internal standard. The drug and internal standard were isolated from plasma by extraction with dichloromethane and 2 M hydrochloric acid. Chromatographic separation was performed on a C₁₈ column with methanol_water (68:32, v/v) adjusted to pH 3.2 with phosphoric acid as mobile phase. The oxidation potential for detection was established by constructing a voltammogram for diclofenac. The quantification limit for diclofenac in plasma was 5 ng mL⁻¹. Linearity of the method was confirmed in the range 5_2000 ng mL⁻¹, correlation coefficient 0.9998. Within‐day relative standard deviations (RSDs) ranged from 0.66 to 14.00% and between‐day RSDs from 0.59 to 15.78%. The method was successfully applied for the determination of pharmacokinetic parameters after ingestion of a 50 mg dose of diclofenac. Studies were performed on 18 healthy volunteers of both sexes. Copyright © 2005 John Wiley & Sons, Ltd.