gabriel hancu

Photochemical degradation of drugs can lead to degradation products with potential toxic or allergizing effects for the human body. A significant amount of work has been carried out over the past few decades to clarify the molecular mechanism of photosensitizing processes observed after the administration of certain drugs and exposure to light. There is a close relation between the photosensitizer effect of a drug and its chemical structure. Compounds possessing certain moieties and functional groups in their molecular structure, like aromatic chromophore systems or photo-dissociable bonds that can form free radicals, and consequently are susceptible to have light-induced adverse effects. Photoionization, photodissociation, photoaddition and photoisomerization are the main chemical processes, which can occur during the photochemical decomposition of a pharmaceutical compound. The current study is a short review describing photochemical degradation of certain pharmaceuticals, presenting specific examples from various pharmaceutical classes for the different types of decomposition mechanisms. In vivo methods and clinical tests available for the investigation of photosensitizing reactions are also discussed.

Cardiovascular diseases (CVDs) are the leading cause of mortality worldwide and are usually multifactorial medical conditions. Usually cardiovascular patients must follow a complicated treatment scheme, containing several drugs. Fixed dose combinations (FDCs) are pharmaceutical formulations containing two or more active ingredients in a one pill. FDCs can add multiple benefits to the treatment of CVDs including increased patient compliance, elimination of some side effects and the simultaneous blockage of multiple pathogenic links. The great prevelance of FDCs in modern therapy brings the necessity of developing new analytical methods for the simultaneous analysis of their components. Capillary electrophoresis (CE) was shown to be as a complementary and attractive alternative to the more frequently used chromatographic methods. CE advantages relate to the high efficiency of separation, rapid method developement, short analysis time and relatively low operational costs. The most frequently used CE techniques in the analysis of FDCs are capilllary zone electrophoresis (CZE) for ionized analytes and micellar electrokinetic chromatography (MEKC) for neutral ones. The current article reviews application of CE in the analysis of FDCs used in the treatment of CVDs.

Currently cardiovascular disease is the leading cause of mortality worldwide, resulting in approximately one third of all deaths globally. In order to address the role that hypertension plays in the morbidity and mortality of cardiovascular diseases, there is an urgent need for a paradigm shift in global hypertension management and treatment. Obtaining target pressure levels using monotherapy can be a difficult task especially in the case of patients with other associated diseases; consequently modern therapeutic guides recommend combinations of two ore more antihypertensives. Fixed dose combinations associate two or more pharmaceutical substances in a single pharmaceutical formulation; each drug typically working at a separate site, blocking different effector pathways. Compounds that struggle to be efficient in the monotherapy of patients with hypertension often become more effective if combined with another drug; associating drugs with different but complementary mechanism of action often leads to increased therapeutic efficacy. The current review presents the advantages of fixed dose combination and summarizes formulations of common dual, triple combinations used in therapy.

Tramadol is a widely used opioid analgesic frequently prescribed for treatment of moderate to severe, acute and chronic pain. It has a complex mechanism of action, acting both as a central opiate agonist and as a norepinephrine and serotonin reuptake inhibitor. It is a chiral substance, having two chiral centers in its structure and it is used in therapy as a racemic mixture of two of its enantiomers, (S,S)-tramadol and (R,R)-tramadol. In the last 25 years, several analytical procedures have been published in the literature for the achiral and chiral determination of tramadol from pharmaceutical formulations and biological matrices. Among these methods, capillary electrophoresis techniques have proved to be an efficient, reliable and cost-effective solution. The purpose of the present review is to provide a systematic survey to present and discuss the electrodriven methods available in the literature for the achiral and chiral analysis of tramadol.

Relatively few medications are available for the management of obesity and all are indicated as adjuncts to increased physical activity, caloric restriction and lifestyle modification. Among different weight-loss drugs, the most intriguing and controversial class is the one of anorexic amphetamines, due to their high efficiency but also relevant side-effects. Several previously approved anorexic amphetamines like fenfluramine, phenylpropanolamine, phenmetrazine and sibutramine have been withdrawn from the market due to unanticipated adverse effects. Nowadays only four amphetamine derivatives are approved for short-term treatment of obesity: amfepramone, benzphetamine, phendimetrazine and phentermine. The article provides an overview of both the history, and the current status, of the use of amphetamine derivatives in the obesity pharmacotherapy.

Through doping, we understand the use by athletes of substances prohibited by the anti-doping agencies in order to gain a competitive advantage. Since sport plays an important role in physical and mental education and in promoting international understanding and cooperation, the widespread use of doping products and methods has consequences not only on health of the athletes, but also upon the image of sport. Thus, doping in sports is forbidden for both ethical and medical reasons. Narcotics and analgesics, anabolic steroids, hormones, selective androgen receptor modulators are among the most frequently utilized substances. Although antidoping controls are becoming more rigorous, doping and, very importantly, masking doping methods are also advancing, and these are usually one step ahead of doping detection techniques. Depending on the sport practiced and the physical attributes it requires, the athletes will look for one or more of the following benefits of doping: recovering from an injury, increasing body recovery capacity after training, increasing muscle mass and strength, decreasing fat tissue, increasing endurance. Finally, when we look once again at a doping scandal, amazed at how much animosity against those caught can exist; the question is: is it really such a disaster as presented by the media or a silent truth under our eyes, but which many of us have refused to accept?

To describe the chemical structure and characterize physico-chemical properties of organometallic complexes it is necessary to use a complex set of analysis methods. Thus, this review has been compiled as a relevant guide which includes the most commonly used methods of analysis in the study of silver complexes with antibacterial quinolones, compounds with promising biological potential. This selection of analysis methods puts on balance the obtained data and the accessibility of the experimental approach. The steps to follow in order to obtain reliable structural information about organometallic complexes of silver, particularly the silver complexes of antibacterial quinolones, are established and presented in the review.

The majority of modern antidepressants (selective serotonin reuptake inhibitors and selective serotonin and norepinephrine reuptake inhibitors) have one or two centers of asymmetry in their structure; resulting in the formation of enantiomers which may exhibit different pharmacodynamic and pharmacokinetic properties. Recent developments in drug stereochemistry has led to understanding the role of chirality in modern therapy correlated with increased knowledge regarding the molecular structure of specific drug targets and towards the possible advantages of using pure enantiomers instead of racemic mixtures. The current review deals with chiral antidepressant drugs; presenting examples of stereoselectivity in the pharmacological actions of certain antidepressants and their metabolites and emphasizing the differences between pharmacological actions of the racemates and pure enantiomers.

The majority of modern antidepressants (selective serotonin reuptake inhibitors and selective serotonin and norepinephrine reuptake inhibitors) have one or two centers of asymmetry in their structure; resulting in the formation of enantiomers which may exhibit different pharmacodynamic and pharmacokinetic properties. Recent developments in drug stereochemistry has led to understanding the role of chirality in modern therapy correlated with increased knowledge regarding the molecular structure of specific drug targets and towards the possible advantages of using pure enantiomers instead of racemic mixtures. The current review deals with chiral antidepressant drugs; presenting examples of stereoselectivity in the pharmacological actions of certain antidepressants and their metabolites and emphasizing the differences between pharmacological actions of the racemates and pure enantiomers.

The aim of the study was the characterization of the electrophoretic behavior of cephalosporins from different generation having different structural characteristics in order to develop a rapid, simple and efficient capillary electrophoretic method for their identification and simultaneous separation from complex mixtures. Ten cephalosporin derivatives (cefaclor, cefadroxil, cefalexin, cefazolin, cefoxitin, cefuroxime, cefoperazone, cefotaxime, ceftazidime, ceftriaxone) were analyzed by capillary zone electrophoresis using different background electrolyte solutions at different pH values. Electrophoretic mobilities of the analytes were calculated, the influence of the electrophoretic parameteres on the separation was established and the analytical conditions were optimized. Taking into consideration their structural and chemical properties cephalosporins can be detected over a pH range between 6 and 10. The best results were obtained using a buffer solution containing 25 mM disodium hydrogenophosphate - 25 mM sodium dihydrogenophosphate, at a pH – 7.00, + 25 kV voltage at a temperature of 25 °C, UV detection at 210 nm. Using the optimized analytical conditions we achieved the simultaneous baseline separation for seven cephalosporins in less then 10 minutes. Using the described optimized electrophoretic procedures, capillary electrophoresis can be used for the identification and determination of cephalosporins in formulated pharmaceutical products and for their separation from complex mixtures.

Amlodipine is a long acting, dihydropyridine type calcium channel blocker frequently used in the treatment of hypertension and coronary insufficiency. The calcium channel blocking activity resides primarily in the S-amlodipine enantiomer, while R-amlodipine is a potent inhibitor of smooth muscle cell migration. In this study capillary electrophoresis was applied for the enantiomeric separation of amlodipine using different native and derivatized; neutral and charged cyclodextrines as chiral selectors. The effects of pH and composition of the background electrolyte, concentration and type of chiral selector, capillary temperature, running voltage and injection parameters have been investigated. Stereoselective interactions were observed when using α-CD, β-CD, HP-β-CD, RAMEB, CM-β-CD and SBE-β-CD. Optimized separation conditions consisted on a 50 mM phosphate buffer, pH – 3.0, 20 mM RAMEB as chiral selector, + 25 kV applied voltage, 15°C temperature and UV detection at 238 nm. Using the optimized electrophoretic conditions we succeeded the chiral separation of amlodipine enantiomers in approximately 6 minute, the order of migration being R-amlodipine followed by S-amlodipine. The method was successfully applied for the determination of amlodipine enantiomers from commercially available pharmaceuticals. The linearity range, limits of detection and quantification, precision and accuracy were determined and the results obtained confirmed that the method was suitable for this purpose. It can be concluded that the proposed capillary electrophoresis methods can be useful for routine pharmaceutical applications with benefits of its effectivity, simplicity, short analysis time and low consumption of analytes, solvents and chiral selectors.

Carvedilol is administered as a racemic mixture of the R(+)- and S(-)-enantiomers, although it was demonstrated that the two enantiomers exhibit different pharmacological effects and stereoselective pharmacokinetics. The aim of this study was the evaluation of several native and derivatized cyclodextrines as chiral selectors for the separation of carvedilol enantiomers. Stereoselective interactions were observed with four cyclodextrines (β-CD, hydroxypropyl-β-CD, randomly methylated β-CD and sulfobuthyl ether- β-CD). The effects of CD concentration, pH value and composition of the background electrolyte, capillary temperature, running voltage and injection parameters have been investigated. The method was validated for precision of peak-area response, linearity range and limits of detection and quantification. An efficient stereoselective capillary zone electrophoretic method was developed for the determination of carvedilol enantiomers using a simple 25 mM phosphate buffer at a pH = 2.5 and 10 mM β-CD as chiral selector, resulting in baseline separation of the two enantiomers with sharp peaks and relatively short analysis time. Highly satisfactory results were obtained from the analysis of carvedilol from tablets, indicating that the method is suitable for routine analysis of carvedilol in pharmaceutical products.

The antiseptic qualities of aromatic and medicinal plants and their extracts have been recognized since antiquity, while attempts to characterize these properties in the laboratory date back the beginning of the XXth century. In the current study essential oils obtained from Pelargonium roseum (Geraniacea) were analyzed for their antibacterial and antifungal activities. The antimicrobial activity of the Pelargonium essential oil was tested against Gram-negative bacteria (Pseudomonas aeruginosa, Proteus mirabilis, Escherichia coli), Gram-positive bacteria (Staphylococcus aureus, Enterococcus faecalis) and fungi (Candida albicans). Disc diffusion method was used to study antimicrobial activity. Inhibition zones showed that the studied essential oils were active against all of the studied bacteria. In the case of Candida albicans, the complete inhibition of the fungus’s development was observed. In the cases of Pseudomonas aeruginosa and Staphylococcus aureus we observed an inhibition comparable to that obtained by the use of an appropriate antimicrobial substance. The volatile oils exhibited considerable inhibitory effects against all the organisms under test, in some cases comparable with those of the reference antibiotics. There were no considerable differences between the antimicrobial activities of the oil obtained by distillation and commercially available Pelargonium oils.

Indapamide is probably the most frequently prescribed diuretic drug, generally being used for the treatment of hypertension. It contains a chiral center in its molecule; is marketed as a racemic mixture; but there are rather few studies regarding the pharmacokinetic and the pharmacological effect differences of the two enantiomers. Our aim was the development of a simple, rapid and precise analytical procedure for the chiral separation of indapamide enantiomers. In this study capillary zone electrophoresis was used for the enantiomeric separation of indapamide using a systematic screening approach involving different native and derivatized; neutral and charged cyclodextrines as chiral selectors. The effects of pH value and composition of the background electrolyte, capillary temperature, running voltage and injection parameters have been investigated. After preliminary analysis a charged derivatized CD, sulfobuthyl ether- β-CD, proved to be the optimum chiral selector for the enantioseparation. Using a buffer solution containing 25 mM disodium hydrogenophosphate – 25 mM sodium didydrogenophosphate and 5 mM sulfobuthyl ether- β-CD as chiral selector at a pH - 7, a voltage of + 25 kV, temperature 15°C and UV detection at 242 nm, we succeeded in the separation of the two enantiomers in approximately 6 minutes, with a resolution of 4.30 and a separation factor of 1.08. Capillary zone electrophoresis using cyclodextrines as chiral selectors proved to be a suitable method for the enantioseparation of indapamide. Our method is rapid, specific, reliable, and cost-effective and can be proposed for laboratories performing indapamide routine analysis.

The aim of the study was the development of a simple and rapid analytical procedure for the determination of the most frequently used antihistamine derivatives. A capillary zone electrophoretic method was developed for the simultaneous separation of loratadine, desloratadine and cetirizine. Efforts were focused primarly on the optimisation of the experimental parameters: buffer composition and concentration, buffer pH, applied voltage, temperature, injection pressure and time. The optimised parameters for the separation were: 25 mM buffer electrolyte, buffer pH 2.5, voltage + 25 kV, temperature 25 °C, injection pressure 50 mbar, injection time 3 seconds, capillary 48 cm (effective length 40 cm) x 50 m, detection at 240 nm. Under these conditions, the analysis time was below 5 minutes, the order of migration being: desloratadine, cetirizine and loratadine. The developed method was validated in terms of linearity, limits of detection and quantification, intra- and inter-day precision, selectivity and robustness. Capillary zone electrophoresis proved to be a suitable method for the simulatneous determination of the three studied antihistamine derivatives.

The paper describes some thin layer chromatographic procedures that allow simple and rapid separation and identification of penicillins and cephalosporins from complex mixtures. Using silicagel GF254 as stationary phase and selecting different mobile phases we succeeded in the separation of the studied beta-lactamins. Our aim was not only to develop a simple, rapid and efficient method for their separation but also the optimization of the analytical conditions. No system will separate all the beta-lactams, but they could be identified when supplementary information is used from color reactions and/or by using additional chromatographic systems. The right combination of solvent system and detection method allows the identification of the studied penicillins and cephalosporins and can be successfully used in the preliminary analysis beta-lactam antibiotics.

Since its introduction capillary electrophoresis has shown great potential in areas where electrophoretic techniques have rarely been used before, including here the analysis of pharmaceutical substances. The large majority of pharmaceutical substances are neutral from electrophoretic point of view, consequently separations by the classic capillary zone electrophoresis; where separation is based on the differences between the own electrophoretic mobilities of the analytes; are hard to achieve. Micellar electrokinetic capillary chromatography, a hybrid method that combines chromatographic and electrophoretic separation principles, extends the applicability of capillary electrophoretic methods to neutral analytes. In micellar electrokinetic capillary chromatography, surfactants are added to the buffer solution in concentration above their critical micellar concentrations, consequently micelles are formed; micelles that undergo electrophoretic migration like any other charged particle. The separation is based on the differential partitioning of an analyte between the two-phase system: the mobile aqueous phase and micellar pseudostationary phase. The present paper aims to summarize the basic aspects regarding separation principles and practical applications of micellar electrokinetic capillary chromatography, with particular attention to those relevant in pharmaceutical analysis.