Biomedical subjects

Peter Mikus

Publications and source records attributed to Peter Mikus.

8 recordsLinked to original sources

PubMed2006

Simultaneous determination of essential basic amino acids in pharmaceuticals by capillary isotachophoresis.

Capillary isotachophoresis (ITP) in cationic regime of the separation with conductometric detection has been used for the separation and determination of basic amino acids (arginine, histidine, and lysine) in pharmaceutical preparations. Several electrolyte systems of different compositions and pH were examined. The optimized ITP electrolyte system consisted of 10 mmol/L potassium acetate adjusted to pH 4.0 with acetic acid as the leading electrolyte with the electroosmotic-flow (EOF) suppressing additive, 0.2% (w/v) methylhydroxyethylcellulose (m-HEC), and 10 mmol/L beta-alanine as the terminating electrolyte. The proposed electrophoretic method was successfully validated. It was convenient for the sensitive, simple, rapid and highly reproducible assay of these amino acids. Good quantitation was obtained in short analysis times (a single analysis took about 10 min). The minimal sample pretreatment and low running costs make the proposed ITP method a good alternative to commonly used analytical methods. The obtained results suggest that the proposed method is suitable for routine assay of basic amino acids in pharmaceuticals.

Amino Acids, Essential↗

PubMed2005

Enantioselective determination of pheniramine in pharmaceuticals by capillary electrophoresis with charged cyclodextrin.

Cyclodextrin (CD)-mediated capillary zone electrophoresis (CZE) in hydrodynamically closed separation system was developed for the separation and quantitation of pheniramine (PHM) enantiomers. Several parameters affecting the separation were studied, including the type and concentration of chiral selector, carrier cation and counterion, and the pH of the buffer. A high effectivity of oppositely migrating carboxyethyl-beta-cyclodextrin (CE-beta-CD) to separate the PHM enantiomers was demonstrated in detail. The optimized chiral analysis of the antihistamine drug was performed in a buffer consisted of 20 mmol/l epsilon-aminocaproic acid adjusted to pH 4.5 with acetic acid, containing negatively charged CE-beta-CD (2.5 mg/ml) as chiral selector and 0.2% (w/v) methylhydroxyethylcellulose (m-HEC) as an electro-osmotic flow (EOF) suppressor. Acceptable validation criteria for sensitivity, linearity, precision, accuracy/recovery were included. The proposed CZE method was successfully applied to the assay of PHM in pharmaceutical formulations using dioxopromethazine as an internal standard.

Cyclodextrins↗

PubMed2005

Determination of salbutamol in pharmaceuticals by capillary electrophoresis.

A capillary electrophoresis (CE) method for the separation and determination of salbutamol (SAL) in commercial pharmaceuticals was developed. Several parameters affecting the separations were studied including type and concentration of the carrier ion, counter ion, and the pH of the buffer. A hydrodynamically closed CE separation mode employing a 300 mum I.D. capillary, dynamically coated by polymeric buffer additive, provided good performance parameters (precision, accuracy, sensitivity). The obtained results suggest that the proposed method is suitable for routine assay of SAL in pharmaceutical preparations and can be used as an alternative to the conventional open CE mode for this application.

Adrenergic beta-Agonists↗

PubMed2005

Enantioselective analysis of cetirizine in pharmaceuticals by cyclodextrin-mediated capillary electrophoresis.

The present paper demonstrates the potential of cyclodextrin (CD)-mediated CE for the chiral analysis of a drug of zwitterionic nature, viz. cetirizine (CET). Various separation mechanisms were applied and several parameters affecting the separation were studied, including the type and concentration of chiral selector, coselector, and carrier ion, and pH of buffer. The optimal separation conditions were based on a medium buffer pH (approximately 5.2) (migration velocity of CET molecule was near to zero) and a highly substituted CD derivative, sulfated-beta-CD, serving as an analyte carrier in the anionic regime of the separation with suppressed electroosmotic flow. In this way, a baseline enantioseparation, reasonable separation efficiency, and short analysis time could be easily achieved. Acceptable validation criteria for sensitivity, linearity, precision, accuracy, and robustness were obtained using a hydrodynamically closed CE separation system. The proposed method was successfully applied to the enantioselective assay of CET in pharmaceutical formulations using fexofenadine (FEX) as an internal standard.

Journal Article↗

PubMed2005

Determination of fexofenadine in tablets by capillary electrophoresis in free solution and in solution with cyclodextrins as analyte carriers.

Capillary electrophoresis (CE) methods for the determination of fexofenadine (FEX) in commercial pharmaceuticals were developed. It was demonstrated that FEX could be effectively analyzed in free solution cationic CE at low pH. Another analytical approach studied was based on cyclodextrin (CD) modified CE where highly charged CD derivatives served as analyte carriers. In this way, the separation range was spread to physiological pH region and a CE analysis of FEX, present actually in its zwitterionic form, could be accomplished. Several parameters affecting the separations were studied, including the type and concentration of carrier ion, counterion, analyte carrier, and pH of the buffer. The methods based on the free solution CE and CD-modified CE were compared each other, validated, and applied for the determination of FEX in tablets.

Anti-Allergic Agents↗

PubMed2004

Analytical characterization of heparin by capillary zone electrophoresis with conductivity detection and polymeric buffer additives.

A capillary zone electrophoresis (CZE) method for the analytical characterization of intact (high-molecular-weight) heparin was developed. For the first time, a hydrodynamically closed CZE separation system with conductivity detector was used for the separation, detection and quantitation of this highly sulfated, linear polysaccharide. Glycine (25mM) adjusted to pH 9.0 by bis-Tris-propane served as the running electrolyte system. Polymeric additives, polyvinylpyrrolidone (PVP), dextran (DEX), were used to improve the separation selectivity as they strongly retarded the heparin macromolecule while they did not practically influence comigrating inorganic anions. The proposed electrophoretic method was successfully validated. It was convenient for the sensitive, simple, rapid and reproducible assay of heparin in raw materials and isotonic saline. Here, the use of the conductivity detector was advantageous as it allowed heparin to be analyzed without a sample pretreatment. The CZE method should be an alternative to the pharmacopoeial conventional gel electrophoresis having used in the quality control of heparin so far. In addition, it should be convenient to quantitative estimation of heparin present in a preparation used, e.g., as the chiral selector in CE separations.

Buffers↗

PubMed2003

Chiral separation of dioxopromethazine in eye drops by CZE with charged cyclodextrin.

Capillary zone electrophoresis (CZE) with carboxyethyl-beta-cyclodextrin (CE-beta-CD) dissolved in the operating buffer was used for the separation and determination of enantiomers of phenothiazine antihistaminic, dioxopromethazine, in commercial pharmaceutical preparation, eye drops. This chiral selector, negatively charged under given separating conditions (20 mmol/l epsilon -aminocaproic acid, acetic acid, pH 4.5), was effective in enantioresolution of the antihistamine even at its low concentrations (3-6 mg/ml) in the buffer solution. CZE identification and quantitation of the relevant constituents present in the preparation (dioxopromethazine enantiomers, phenylephrine) were based on the response of photometric absorbency detector, operating at a 275 nm detection wavelength. Changes in pH, type and concentration of chiral selector were studied in relation to chiral resolution. Acceptable validation criteria for sensitivity, precision, linearity and repeatability are included.

Cyclodextrins↗

PubMedDate not supplied

COPing with hypoxia.

To understand how cells respond to altered oxygenation, a frequent experimental paradigm is to isolate known components of bona fide oxygen responsive proteins. Recent studies have shown that a protein known as CSN5 or JAB1 interacts with both the HIF-1alpha oxygen-responsive transcription factor and its oxygen-dependent regulator, the Von Hippel-Lindau (pVHL) tumor suppressor. CSN5 is a component of the COP9 Signalosome (CSN) which is a multi-subunit protein that has high homology to the lid of the 19S lid of 26S proteasome. The exact function of the CSN5 interaction with pVHL and HIF-1alpha remains to be fully elucidated, but it is clear that the interaction is both oxygen dependent and that CSN5 may play different roles under oxic and hypoxic responses. Further, evidence has also been published indicating that pVHL can be potentially post-translationally modified by CSN5 (de-neddylation) and that CSN5 transcription is regulated by hypoxia as are many of the key pVHL/HIF-1alpha regulatory genes such as the PHDs and OS-9. This review will give a broad overview of known CSN5 and COP9 Signalosome functions and how these functions impact the pVHL/HIF-1alpha signaling complex and potentially other oxygen-sensitive response networks.

Amino Acid Sequence↗