Onečišćenja u lijekovima

Impurities in pharmaceuticals are the unwanted chemicals that remain with the active pharmaceutical ingredient (API), or develop during formulation, or upon aging of both API and formulated products. Th e presence of these unwanted chemicals even in small amounts may infl uence the effi cacy and safety of the pharmaceutical products. According to the International Conference on Harmonization (ICH) of Technical Requirements for Registration of Pharmaceuticals for Human Use, impurities are classifi ed as organic impurities, inorganic impurities and residual solvents. Impurities can originate from several sources, such as starting materials, synthetic intermediates and by-products, degradation products arising during storage, functional group-related typical degradation, mutual interaction amongst ingredients and formulation- related impurities. Control of stereochemical purity of an API with chiral centers is also necessary. Also, polymorphic forms are sometimes considered as impurities that need to be controlled. Impurity profi ling is the common name of a group of analytical activities, the aim of which is the detection, identifi cation/structure elucidation and quantitative determination of organic and inorganic impurities, as well as residual solvents in bulk drugs and pharmaceutical formulations. Since this is the best way to characterize the quality and stability of bulk drugs and pharmaceutical formulations, this is the core activity in modern drug analysis. Highly sophisticated analytical techniques, such as chromatographic, spectroscopic and hyphenated techniques, are inevitable tools in the detection, identification, characterization and quantification of impurities

Kapilarna elektroforeza u farmaciji

Capillary electrophoresis is a new separation technique. It is an analytical technique that usually complements or replaces high performance liquid chromatography. Basic principle of the technique is the migration of charged species under applied electric field towards one of the electrodes through a narrow capillary filled with electrolyte solution. Main advantages over other chromatographic methods are short analysis time, high efficiency, small sample and solvent volumes, low costs, simplicity and ecological acceptability. Capillary electrophoresis has several modes of separation which allows analysis of different types of analytes. Capillary electrophoresis has found its application in the drug analysis of large molecules like proteins, peptides and nucleic acids, small organic molecules such as drugs, hormones, plant metabolites, food product ingredients, small inorganic ions etc. It is a method of choice when rapid results are needed. Capillary electrophoresis has become the predominant technique for the analysis of both basic and chiral pharmaceuticals, it is unavoidable in biotechnology and promises to be a valuable tool in troubleshooting in proteome-wide analysis, DNA sequencing and genotyping. Despites of all advantages and application possibilities, capillary electrophoresis is still not enough explored and used in routine analysis. A review of different capillary electrophoresis techniques principles and applications in pharmacy is presented in this article

Kinetika površinske redoks reakcije 2-hidroksi-5-[(4-sulfofenil)azo]benzojeve kiseline

The standard surface redox reaction rate constant of the quasireversible electroreduction of 2-hydroxy-5-[(4-sulfophenyl)azo]benzoic acid adsorbed on the static mercury drop electrode has been determined as ks = 24 (± 6) s–1 using the method of split square-wave voltamograms.Rabeći metodu rascijepljenih pravokutnovalnih voltamograma, određena je standardna konstanta brzine površinske redoks reakcije (ks = 24 (± 6) s–1) kvazireverzibilne elektroredukcije 2-hidroksi-5-[(4-sulfofenil)azo]benzojeve kiseline adsorbirane na površini statične živine kapi

Identifikacija monakolina i citrinina u crvenoj fermentiranoj riži primjenom LC/MS/MS tehnike

Red fermented rice, also known as red yeast rice, Hongqu, Anka or red Koji, is the fermented product of rice on which red yeast (Monascus purpureus) has been grown. For a thousand of years it has been used in China to make rice wine, as a food preservative for maintaining the color and taste of fish or meat and as a traditional medicine for digestive and vascular function. A complete and detailed description of its manufacture and medicinal properties are found in the ancient Chinese pharmacopoeia, published during the Ming Dynasty (1368–1644 a.d.). Over the past decade, there has been increased scientific interest in red yeast rice, as an alternative therapy for hyper cholesterolemia. Many studies have demonstrated that red yeast rice may be especially useful for treating patients who refuse to take statin drugs because of philosophical reasons or patients who are unable to tolerate statin therapy due to statin-associated myalgias. The major components found in red yeast rice, known as monacolins (polyketides), are reported to exhibit a cholesterol lowering action by inhibiting the 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase. Still, it is believed that the hypolipidemic effect of red yeast rice cannot be accounted for only by the monacolins, but by a synergy of all other components present in red yeast rice: plant sterols, isoflavones and isoflavone glycosides, selenium and zinc. The most important toxic component in red fermented rice is citrinin, a mycotoxin produced by red yeast (Monascus purpureus). It has been known to cause kidney and liver damage in humans. Therefore, Japan has issued an advisory limit of 200 ppb while the European Union has a recommended limit of 100 ppb. The aim of our work was to develop a new LC/MS/MS method for identification of active components, monacolin K (lovastatin) and monacolin K acid and toxic component, citrinin, present in red yeast rice capsules

Analiza kiralnih lijekova kapilarnom elektroforezom

The importance of enantiomer purity control was perceived in 1960s after the Thalidomide disaster. Enantiomers can show different pharmacological efficiency, bioavailability and therapeutic indications. Very often only one enantiomer is active, while the other can have no activity whatsoever, or can even be toxic. Therefore, methods that enable separation and purity evaluation of enantiomers are very important. Most often used techniques are polarimetry, circular dichroism, roentgen diffraction and chiral chromatography. Separation techniques frequently used are high performance liquid chromatography, gas chromatography and capillary electrophoresis. Capillary electrophoresis is a very fast and cheap technique. The most often used chiral separators in capillary electrophoresis are ciclodextrins. They are cyclic oligosaharyds, composed of a-D-glucopyranoside units bound together in a ring. Topologically cyclodextrins are represented as toroids with the larger and the smaller openings of the toroid exposing to the solvent secondary and primary hydroxyl groups respectively. The exterior of the toroid is hydrophilic making it water soluble, while the interior is relatively hydrophobic. This enables the cyclodextrin to form inclusion complexes with drug molecules. One of the enantiomers forms stronger interactions with cyclodextrin then the other cyclodextrin, which ensures enantiomer separation. Enantioselective capillary electrophoretic method using cyclodextrins are used in pharmaceutical analysis, cosmetic and food industry, in forensic science and in environmental protection. In pharmaceutical analysis they are used for determination of stereochemical purity, especially when it is necessary to quantify one of the enanitomers in the presence of large quantity of other stereoisomers

Razvoj i validacija HSS-GC-FID metode za određivanje sadržaja lakohlapljivih sastavnica sirupa za iskašljavanje za djecu

A cough syrup is a medicinal product used in an attempt to treat coughing and related conditions. Traditional herbs are used for preparation of cough syrup. There are two main categories of herbs that are used in preparation of cough remedies: expectorants and antitussives. For productive coughs, treatment with expectorants may be attempted to loosen mucus from the respiratory tract. For dry coughs antitussives are used to suppress the body’s urge to cough. Herbal medicinal products may contain significant levels of ethanol arising from its use as an extraction solvent in liquid extracts and tinctures. Although the use of ethanol is necessary for extraction of pharmacologically active compounds, it was found that some herbal medicinal products contain large amounts (up to 60 %) of ethanol with even less clinical need or benefit. In young children ingestion of even modest amounts of ethanol may lead to permanent neurological damage as result of hypoglycemia. Therefore, special attention should be given to the ethanol content of herbal medicinal products for pediatric use. At the moment the safety evaluation of the ethanol content of herbal medicinal products for pediatric use is not harmonized between different European Union Member States. Moreover, the lack of guidelines relating to safe limits of ethanol as part of herbal medicinal products for pediatric use has also led to different national labeling practices. Therefore, the aim of our work was to develop and validate a new HSS-GC-FID method for quantification of ethanol and its main impurity, methanol, present in children’s cough syrup

Capillary Electrophoresis Determination of Pravastatin and Separation of Its Degradation Products

A capillary zone electrophoresis method for pravastatin determination was developed and validated. Rapid migration of negatively charged pravastatin molecule was obtained in alkaline buffer by the application of electric field of 30 kV. Influence of the pH value and ionic strength of running buffer, applied voltage and capillary temperature on mobility and sensitivity was evaluated. Detection wavelength was set to 237 nm. The method was applied to the determination of the drug in pharmaceutical dosage form. Pravastatin is a δ-hydroxy acid, which is prone to lactonize and epimerize in a pH-dependent manner. Micellar electrokinetic chromatographic approach was chosen to develop a method able to separate pravastatin and its degradation products in acidic media. The proposed method allows baseline separation of hydroxy acid and neutral lactone forms of the drug that appear as interconversion products depending on the pH value

Thermoanalytical, Spectroscopic and Chromatographic Approach to Physicochemical Compatibility Investigation of 5-Aminosalicylates and Folic Acid

Fixed-dose combinations have shown to be a great alternative to traditional polytherapy; however, development of such formulation requires thorough physicochemical compatibility investigation of active pharmaceutical ingredients to provide a stable, safe and therapeutically effective product. In this work, differential scanning calorimetry, X-ray powder diffraction, isothermal stress testing followed by Fourier-transform infrared spectroscopy and chromatographic analysis as well as dissolution studies were used for physicochemical compatibility investigation of folic acid and balsalazide or olsalazine. Balsalazide and olsalazine as well as their blend were successfully characterised regarding their physicochemical properties using the mentioned techniques. Differential scanning calorimetry gave ambiguous results due to premature degradation of balsalazide. On the contrary, other techniques have implied the absence of any chemical reactions or physical changes in prepared blends. Obtained result imply that folic acid is compatible with both balsalazide and olsalazine which goes in favour of developing proposed fixed-dose combinations. This work is licensed under a Creative Commons Attribution 4.0 International License