Agnieszka Sobczak

Analysis of Sartans: A Review

The risk of cardiovascular diseases is closely related to hypertension, high cholesterol levels, and diabetes. When these risk factors appear together they are referred to as a metabolic syndrome. In the treatment of cardiovascular diseases, a combination of antihypertensive, hypolipemiant, and antidiabetic drugs is often applied. Diuretics (chlortalidone, hydrochlorothiazide, etc.) and angiotensin II receptors antagonist (sartans) are used to control hypertension, whereas statins (fluvastatin, simvastatin, etc.) are used to reduce cholesterol levels. This review is concerned with methods for the analysis of sartans in various matrices, such as pharmaceutical formulations, environmental and biological samples, and discusses the current status of stability studies of sartans . It also presents analytical methods for the simultaneous determination of sartans, diuretics, and statins.

Electrocatalysis of NADH oxidation using electrochemically activated fluphenazine on carbon nanotube electrode.

Electrocatalytic determination of NADH using a hybrid surface-modified electrode with multi-wall carbon nanotubes (MWCNTs) and a novel electrogenerated redox mediator is described. The redox mediator precursor - fluphenazine (Flu) was adsorbed on MWCNT-modified glassy carbon (GC) electrode which was then subjected to electrochemical activation in 0.1 M H2SO4 using cyclic voltammetry (CV) over a range of potentials -0.2 to 1.5 V vs. Ag/AgCl (6 scans at 100 mV s(-1)). Cyclic voltammograms of Flu indicated the formation of a stable electroactive material presenting one reversible redox couple at the formal potential of -0.115 vs. Ag/AgCl in a phosphate buffer (pH7.0) as a supporting electrolyte. The peaks increased linearly with increasing scan rate indicating electroactive molecules anchored to the electrode surface. The GC/MWCNT/Flu electrode efficiently catalyzed the oxidation of NADH with a decrease in the overpotential of about 600 mV and 150 mV compared to the bare GC and GC/MWCNT electrode, respectively. This modified electrode was successfully used as the working electrode in the chronoamperometric analysis. The peak current response to NADH was linear over its concentration range from 15 μM to 84 μM, and correlation coefficient 0.998. The limits of detection (5 μM) and quantitation (15 μM) were evaluated.

Stability of epidoxorubicin in solid state.

The influence of temperature and relative air humidity on the stability of epidoxorubicin hydrochloride (EP) was investigated. The degradation of the substance studied was determined: (a) in dry air at 393K, (b) at relative air humidity ~76% at 333K, 343K, 353K, 363K and 373K, (c) in the relative air humidity range 50-90% at 363K. The degradation of EP in the atmosphere of increased relative air humidity was a first-order reaction relative to substance concentration and in dry, hot air (RH 0%; 393K) is a reversible first-order reaction relative to substance concentration. The dependences lnk=f(1/T) and lnk=f(RH%) were described by the equation: lnk=(35.1±10.9)-(16,250±3823)(1/T) and lnk=(3.79±3.34) × 10(-2) (RH%)-(12.9±2.4), respectively. The kinetic and thermodynamic parameters of EP degradation were calculated. The parameters of separation were following: LiChrospher RP-18 column, 5 μm, 250 mm × 4 mm; mobile phase: the mixture of equal volume of acetonitrile and the solution containing 2.88 gl(-1) of sodium laurisulfate and 2.25 ml l(-1) of phosphoric acid (V) 85%; flow rate: 1.0 ml min (-1); UV detection - 254 nm.

Determination of adamantane derivatives in pharmaceutical formulations by using spectrophotometric UV-Vis method.

A simple and sensitive extractive spectrophotometric method have been developed and validated for determination of amantadine hydrochloride (AM), memantine hydrochloride (MM) and rimantadine hydrochloride (RM) in pure and pharmaceutical formulations. The method is based on the reaction of these active compounds with bromophenol blue (BB) in acetate buffer (0.1 M) pH 3.5 to form an orange-colored products which have absorption maxima at 408 nm. The procedure of complexation was optimized with regard to such factors as concentrations of BB, pH of medium, a kind of extracting solvents and a number of extractions. Under the optimum conditions, linear relationships A408 = f(c) with good correlation coefficients (≥0.996) and low limit of detection were obtained in the ranges of 50.0–220.0 µg·mL−1, 20.0–150.0 µg·mL−1 or 10.0–110.0 µg·mL−1 for AM, MM and RM, respectively, for the spectrophotometric methods. The proposed method could be applied to the determination of AM, MM and RM in dosage forms. The recovery was 95.3–101.9%. The method was linear, precise and accurate.

New fluphenazine analogue with antimutagenic and anti-multidrug resistance activity—degradation profile and stability-indicating method

Hydrochloride of 10-{2-hydroxy-3-[N,N-bis-(2-hydroxyethyl)amino]propyl}-2-trifluoromethylphenothiazine (Flu-A) is a analogue of neuroleptic fluphenazine. Flu-A exhibits anti-multidrug resistance, antimutagenic, proapoptopic, and cancer-chemopreventive activities in screening studies. To define identity, quality, and purity of new active substance it is necessary to develop a appropriate analytical method and to establish a degradation profile. Thus, a stability-indicating reversed-phase high-performance liquid chromatography method was developed and validated for quantitative determination of Flu-A in the presence of its degradation products generated under stress conditions. The compound was subjected to oxidation, photolysis, and degradation in aqueous solutions (neutral and acidic), and solid state according to the International Council for Harmonisation Guidelines. The method was also found to be suitable for intermediate and accelerated studies and for the evaluation of kinetic mechanism of Flu-A degradation in aqueous solutions (pH 5.1–7.5, 353 K). The structures of main potential degradation products were established using high-performance liquid chromatography-Electrospray Ionization-mass spectrometry method.

Stability of Epidoxorubicin Hydrochloride in Aqueous Solutions: Experimental and Theoretical Studies

The first-order degradation kinetics of epidoxorubicin were investigated as a function of pH, temperature, and buffers concentrations. The degradation was followed by HPLC. Buffer catalysis was observed in acetate and phosphate buffers. The pH-rate profiles were obtained at 333, 343, 353, and 363 K. The pH-rate expression was , where , , and are the second-order rate constants (mol−1 L s−1) for hydrogen ion activity and for hydroxyl ion activity, respectively, and and are the first-order constants (s−1) for spontaneous reaction under the influence of water. Epidoxorubicin demonstrates the greatest stability in the pH range 3–5. The electrostatic molecular potential orbitals HOMO-LUMO were also defined in order to determine the cause of the reactivity of particular epidoxorubicin molecule domains in solutions with various pH values.

Basic Studies on Chemopreventive Properties of Quercetin and Curcumin and Other Plant-origin Compounds in Ovarian Cancer Cells-A Mini-review

Despite the increasing number of studies on the molecular actions of quercetin and curcumin, their anticancer efficacy, safety and molecular aspects of chemopreventive action in the ovarian cancer prophylaxis or treatment and also their potential in the sensitization to cytostatics used in the clinical practice remains still not clearly understood. Based on basic studies we have summarized evidences for inhibitory activities of several often studied plantorigin bio-active compounds (mostly quercetin and curcumin) against ovarian cancer cells proliferation, their mechanisms of action as well as their strong potential to sensitization of ovarian cancer cells to the presence of several platinum-based cytostatics - cisplatin and oxaliplatin. Up to date only several dietary, clinical (cohort and case–control) studies evaluating the association of some flavonoids (mostly nonisoflavones) and its subgroup components consumption and ovarian cancer risk were already performed. According to the researchers, there has been no association between ovarian cancer risk and total nonisoflavone flavonoids intake. There is a still an insufficient amount of data designed to explain the effect of quercetin or curcumin (alone or together) on ovarian cancer development and/or its chemotherapy. Obtained results provide limited support for an association between nonisoflavone flavonoids intake and ovarian cancer risk, therefore there is a need for further and more accurate studies to be confirmed. We are of the opinion that this paper will contribute to a better understanding of the molecular basis for positive interactions between concomitant usage of quercetin or curcumin with above-mentioned cytostatics and other bio-active agents. This work may also contribute to an increase in the number of preclinical studies or other clinical, dietary trials using these or other phenolic / alkaloid, plant-origin constituents in order to investigate efficiency and safety of pharmacotherapy of ovarian cancer patients.