Category Archives: AMM 2017, Volume 63, Number 2


DOI: 10.1515/amma-2017-0019

By the request of corresponding author Fogarasi Erzsébet, the article „Could Codeine Containing OTC Analgesics Sold in Romania be Used as Recreational Drugs?” published in Acta Medica Marisiensis, 2016;62(3):309-312 (DOI 10.1515/amma-2016-0031) was retracted, due to identified Conflicts of Interest.
As an immediate consequence of the aforementioned retraction, the accompanying editorial “The Culprit Coffee Filter and Freezer?” published in Acta Medica Marisiensis, 2016;62(3) had to be retracted for lack of object. This does not mean that we deny or back off the content of the editorial.

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Fresh or Frozen Berry Fruits?

Recent studies suggest that diet rich in fruits and vegetables could be associated with reduced risk of coronary hard disease, stroke and even cancer [1]. Both fruits and vegetables are important sources of vitamins (e.g. group of vitamins B and C), minerals and fibers. Berry fruits are considered the healthiest, being also called the “super fruits”. They are rich in anthocyanins, catechins, ellagic acid, vitamin C, flavonoids and antioxidants.
Catechins are flavonols that support the antioxidant defense system, while anthocyanins (water-soluble colored pigments that depending on their pH, could have red, blue or purple color) are associated with a low risk of certain cancers, prevent aging, improve memory function and the urinary tract health. Both catechins and anthocyanins have antioxidant properties [2].
Antioxidants are substances that protect the body by neutralizing free radicals or unstable molecules of oxygen that are major sources of disease and aging and can damage the body cells. They reduce the inflammation, neurodegenerative oxidative stress and macular degeneration, improve cardiovascular functions and decrease the risk of cancer. [More]

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Letrozole Determination by Capillary Zone Electrophoresis and UV Spectrophotometry Methods

DOI: 10.1515/amma-2017-0022

Objective: Letrozole is a highly potent oral nonsteroidal aromatase inhibitor triazole derivative. The aim of this study was to quantify letrozole from bulk, pharmaceutical formulation, and spiked urine samples by developing a simple, rapid and cost effective capillary electrophoresis method. Methods: A capillary zone electrophoresis method was optimized and validated. Additionally, an UV spectrophotometry method was used for comparing results. Results:The capillary zone electrophoresis method using a 90 mM sodium tetraborate background electrolyte proved to be an efficient method for determination of letrozole in a very short time, less than 2 minutes, using 20 kV voltage, 50 mbar/2 seconds pressure and 50°C temperature as optimum parameters. Additionally, the UV spectrophotometry method proved to be simple and efficient to quantify letrozole from bulk material and pharmaceutical formulation with linearity of response between 5 to 20 µg·mL-1 concentrations. For both methods, validation parameters, including linearity, detection and quantification limits were determined. Also we proved that our electrophoretic method has potential in analyzing letrozole from biological samples, obtaining encouraging results on estimation of letrozole from spiked urine samples without any special treatment. Conclusions: To quantify letrozole from bulk material, pharmaceutical preparations, and spiked urine samples the capillary zone electrophoresis method using a tetraborate sodium background electrolyte has proven to be simple and appropriate. Also a simple UV spectrophotometric method has been developed and validated for the same purposes.

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The Influence of CYP2D6 Phenotype on the Pharmacokinetic Profile of Atomoxetine in Caucasian Healthy Subjects

DOI: 10.1515/amma-2017-0023

Objective: To analyze a potential phenotypic variation within the studied group based on the pharmacokinetic profile of atomoxetine and its active metabolite, and to further investigate the impact of CYP2D6 phenotype on atomoxetine pharmacokinetics.
Methods: The study was conducted as an open-label, non-randomized clinical trial which included 43 Caucasian healthy volunteers. Each subject received a single oral dose of atomoxetine 25 mg. Subsequently, atomoxetine and 4-hydroxyatomoxetine-O-glucuronide (glucuronidated active metabolite) plasma concentrations were determined and a noncompartmental method was used to calculate the pharmacokinetic parameters of both compounds. Further on, the CYP2D6 metabolic phenotype was assessed using the area under the curve (AUC) metabolic ratio (atomoxetine/ 4-hydroxyatomoxetine-O-glucuronide) and specific statistical tests (Lilliefors (Kolgomorov-Smirnov) and Anderson-Darling test). The phenotypic differences in atomoxetine disposition were identified based on the pharmacokinetic profile of the parent drug and its metabolite.
Results: The statistical analysis revealed that the AUC metabolic ratio data set did not follow a normal distribution. As a result, two different phenotypes were identified, respectively the poor metabolizer (PM) group which included 3 individuals and the extensive metabolizer (EM) group which comprised the remaining 40 subjects. Also, it was demonstrated that the metabolic phenotype significantly influenced atomoxetine pharmacokinetics, as PMs presented a 4.5-fold higher exposure to the parent drug and a 3.2-fold lower exposure to its metabolite in comparison to EMs.
Conclusions: The pharmacokinetic and statistical analysis emphasized the existence of 2 metabolic phenotypes: EMs and PMs. Furthermore, it was proved that the interphenotype variability had a marked influence on atomoxetine pharmacokinetic profile.

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Analytical Methodologies for the Stereoselective Determination of Sibutramine: An Overview

DOI: 10.1515/amma-2017-0021

Sibutramine is a chiral anti-obesity drug which decreases food intake and increases energy expenditure. In therapy it is used as a racemic mixture; however both pharmacokinetic and pharmacodynamic data have revealed enantioselective behavior of sibutramine and its major active metabolites. Several chromatographic and electrophoretic analytical methods have been published so far for the chiral determination of sibutramine from pharmaceutical preparations and biological samples. The current paper aims to provide a systematic review of the stereochemical aspects and analytical methods used for the enantiodetermination of sibutramine and its active enantiomers covering the last 15 years.

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Silver Cation Coordination Study to AsW9 Ligand – A Trilacunar Arsenotungstate Compound

DOI: 10.1515/amma-2017-0018

Objective: The main objective of this research is to find the coordination ratio between AsW9 and Ag+, as a preliminary study for synthesizing a new silver-arsenotungstate complex.
Material and method: The ligand:cation molar ratio in complexes was determined by conductometric and potentiometric titrations of AsW9 with silver salts: CH3COOAg, AgNO3.
Results: The ratio was obtained from the inflexion points of the curves when molar ratio was plotted versus conductivity, or from the equivalence point when silver added volume was plotted versus pH value. Each graphic shows one point of inflexion corres ponding to 1:1.54 ratio of AsW9:Ag+. In the same manner, the equivalent volumes determined by graphical method gave the ratio 1:1.53. The spectral results confirmed that a AsW9:Ag+ complex was formed since the ligand absorption maxima values have been changed from 190 nm to 197 nm in the case of using AgNO3 and 196 nm for CH3COOAg corresponding to the W=Od bond, and from 246,5 nm to 274 nm (AgNO3) and 270 nm (CH3COO-Ag+) for the W-Ob,c-W bond.
Conclusions: Silver cation exhibit a preference for AsW9 in a ratio of 3 to 2. This ratio can be associated to a sandwich type arrangement, with two trilacunary Keggin building blocks incorporating 3 metal cations in a tetrahedral geometry.

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Flow Cytometry Assessment of Bacterial and Yeast Induced Oxidative Burst in Peripheral Blood Phagocytes

DOI: 10.1515/amma-2017-0020

Objective: The aim of this study was to verify in our laboratory conditions the performance criteria of a commercial kit (PhagoburstTM, Glycotope Biotechnology) as described by the producers. We have also partially altered the use of the available kit by introducing a non-opsonized Candida albicans stimulus, in addition to the opsonized Escherichia coli stimulus provided by the manufacturer.
Material and methods: The peripheral blood samples of 6 clinically healthy adults were tested in triplicate according to the manufacturer recommendations. The intra-assay imprecision, as well as the ranges of neutrophil and monocyte burst activation triggered by various stimuli, were assessed.
Results: The activation range of granulocytes and monocytes was similar to the one described by the producer in the presence of E. coli (granulocytes: 78.45-99.43% versus 99.6-99.95%, average %CV of 1.53% versus 0.1%, monocytes: 54.63-92.33% versus 81.80-96.67, average %CV 6.92% versus 1.1%). The leukocyte range of activation in the presence of non-opsonized C. albicans was comparable to the one triggered by the fMLP (N-formyl-methionyl-leucyl-phenylalanine) stimulus.
Conclusion: The intra-assay precision obtained in our laboratory conditions, as well as the ranges of activated leukocytes, are comparable to the ones described by the producer when using E. coli as a stimulus. The present study shows that introducing an extra fungal stimulus for burst oxidation assessment could provide additional information regarding the non-specific cellular immune response, particularly in patients at risk for candidemia.

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The Risk of Using Poppy Seed Tea Made from Several Varieties Available on the Romanian Market

DOI: 10.1515/amma-2017-0013

Objective: the number of alkaloids like morphine and codeine found in poppy seeds used in food industry are monitored by a directive given by European Food Safety Authority. Based on this regulation the aim of the study was to determine the quantity of morphine and codeine from several brands of poppy seeds.
Methods: an HPLC-UV method (205 nm) was developed to measure the quantity of morphine and codeine. Sample preparation was made using recipes posted on Drugs Forum by some users. Limits of detection were not determined because the lowest concentration from the reference (0.1 µg/ml) detected morphine concentrations that are far lower than a limit of toxicological concern.
Results: The concentrations, which were found, ranged between Below the Level of Toxicological Concern (BLTC) – 243.26 mg/kg for morphine and BLTC – 88.58 mg/kg for codeine using several methods of preparation.
Conclusions: one can observe that there are some brands of poppy seeds which do not respect the regulation about the amount of morphine and codeine. The high amount of morphine in some samples suggests that there are different varieties of poppy seeds, which can be used for an illicit purpose and can lead to addiction or even overdose in some cases.

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Preparation and Characterization of Levofloxacin-Loaded Nanofibers as Potential Wound Dressings

DOI: 10.1515/amma-2017-0014

Objective: The study aimed at obtaining and characterizing levofloxacin-loaded, poly(ε-caprolactone) electrospun nanofiber formulations to be used as antibacterial wound dressings.
Methods: Drug-loaded nanofibers were obtained by the electrospinning process and their morphology was determined using scanning electron microscopy. Structural analysis of the prepared nanofibers was carried out using differential scanning calorimetry and dissolution testing was performed in order to determine drug release.
Results: Both nanofiberous formulations (containing 20 % and 50 % w/w levofloxacin) showed dimensions in the range of few hundred nanometers. Thermograms indicated that the formulation containing 20% levofloxacin was totally amorphized, showing a rapid release of the active, in 20 minutes.
Conclusions: The poly(ε-caprolactone)-based electrospun nanofibers, containing levofloxacin presented suitable characteristics for obtaining potential antibacterial wound dressings.

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