Full Journal №4 (2016)

UDC 615.07

Leontiev D.A., Gryzodub O.I., Volovyk N.V.

State Enterprise «Ukrainian Scientific Pharmacopoeial Centre for Quality of Medicines»

Revision of the National Part to the General Text 5.12. «Reference Standards» to be included in Supplement 1 to the 2d Edition of the State Pharmacopoeia of Ukraine

The expediency of revising the national part to the General Text 5.12 «Reference Standards» of the State Pharmacopoeia of Ukraine (SPU) was shown. A comparative analysis of the texts of the European Pharmacopoeia and SPU in terms of terminology for the pharmacopeial reference standards (PhRS) was conducted. The explanation about the conformity of the terms used by the European Pharmacopoeia and SPU regarding reference standards was given. The status of SPU PhRS was clarified. Reference standards of the European Pharmacopoeia are official for quality control of medicines described in the European Pharmacopoeia; in all other cases, SPU PhRS are official. If a national SPU monograph exercises texts retrieved from the monographs of the United States Pharmacopoeia (USP) or British Pharmacopoeia (BP), reference standards of corresponding pharmacopoeias (USP RS or BP CRS) may be used as official along with SPU PhRS; in this case, a link to the corresponding reference standard is given in the monograph. SPU PhRS are characterised using the principle of insignificance of the uncertainty for the assigned values of reference standards. With high reliability, the same conclusion about quality of an analysed medicinal product can be made whether SPU PhRS or those of other pharmacopoeias are used. The statement significant for users that in routine analysis, SPU PhRS can be used instead of reference standards of the European Pharmacopoeia has been introduced. However, in case of doubt about the test results or dispute between the parties, official reference standards should be used. It was explained that users are provided with all necessary information for correct use of SPU PhRS in non pharmacopeial procedures. Information about the uncertainty of assigned value of SPU PhRS and clearly defined metrological approaches to certification and use of reference standards allows users to control the risk of making an incorrect decision about quality of medicinal products. In addition, it enables them to certify working reference standards for quantitative tests metrologically correctly. Terms of use of working reference standards were clarified. Theses uninformative for users were excluded. On the basis of this work, a new version of the national part to the General Text 5.12 «Reference Standards» to be included in Supplement 1 to the 2d Edition of the State Pharmacopoeia of Ukraine was developed.

Keywords: pharmacopoeial reference standards, terminology, metrological aspects of use, accompanying documentation, working reference standards, General Text 5.12, national part, the State Pharmacopoeia of Ukraine.


UDC 615.687.5

Georgiyevskiy G.V.

State Enterprise «Ukrainian Scientific Pharmacopoeial Center for Quality of Medicines»

The main trends in the harmonization of the requirements of production and quality control of cosmetic products in Ukraine with EU requirements in the light of membership of Ukraine in European Pharmacopoeia

For discussion for all pharmaceutical community on the basis of the stated approach to cosmetic means in the EU and France, as well as the state regulatory framework in Ukraine submitted key questions. In 1997, the Ukraine Pharmacopoeial Center received the status of Observer to the European Pharmacopoeia, the first of all former USSR countries. In 2001 issued by the State Pharmacopoeia of Ukraine, harmonized with EP. In 2013, the Ukraine Pharmacopoeial Center became a full member of the European Pharmacopoeia. This implies the recognition on the territory of Ukraine of the requirements of the EP to the quality of drugs. Organizational European Pharmacopoeia is created by participating countries on the basis of the European Directorate for the Quality of Medicines (EDQM). This implies that the goals and objectives of the Ukraine Pharmacopoeial Center, the structure must match what is in EP, i.e. EDQM. Considered the question of the regulation of cosmetic products in the EU and France, as one of the three «pillars» of the EU. In the European Pharmacopoeia does not contain monographs on cosmetics (such as in the French Pharmacopoeia, the Pharmacopoeia of the United States, China Pharmacopoeia, the UK Pharmacopoeia), but, nevertheless, work on the harmonization of the requirements in the various EU countries require the creation of a working group (it exists in EP) for clinical trials and progressive therapy.

Keywords: cosmetics, pharmaceuticals, The State Pharmacopoeia of Ukraine, European Pharmacopoeia, the regulatory framework of cosmetic products.


UDC 615.074:542.3

Dmitriieva M.V., Lukianova I.S., Pashko V.V.

State Enterprise «Ukrainian Scientific Pharmacopoeial Center for Quality of Medicines» LLC «Donau Lab Ukraine»

The test sample of isopropyl alcohol attestation within the Professional Testing Scheme for laboratories

The test sample attestation was carried out for the test assignment «Isopropyl alcohol identification based on the relative density» of the 12th round of the Professional Testing Scheme (PTS) for medicines quality control laboratories. The substance of isopropyl alcohol which meets the pharmacopoeial requirements was selected and certified as the test sample for PTS. The sample attestation was conducted in concordance with the requirements of the Ph. Eur. / SPU monograph «Іsopropyl alcohol». The determination of relative density was performed using either a pycnometer or a densitometer. The test sample certification criterias were developed. According to established criterias and on the basis of the obtained results, the possibility for objective and reliable identification of the test sample on the basis of its relative density was confirmed. The homogeneity of the test sample and its stability during the evaluation and throughout the round were verified. The certified value of the relative density of the test sample was assumed and the permissible deviation for the results of participants from the certified value was defined.

Keywords: Professional Testing Scheme, attestation, test sample, relative density, isopropyl alcohol.


UDC 615.32:(543.544.943.3+544.022.532)

Andruchenko T.L., Verushkin О.G., Kulikov A.Yu.

State Enterprise «Ukrainian Scientific Pharmacopoeial Center for Quality of Medicines», Kharkіv

Assay of total capsaicin contents in fruit and extract from Capsicum annuum by micellar thin-layer chromatography

The TLC method for quantitative estimation of total capsaicin contents in red pepper and red pepper extract was developed and validated. Method allows using for separation the normal phase plate ALUGRAM SIL G/UV254 and micellar mobile phase that contains isopropanol – 0.1 M Tween-80 solution – 0.1 M cetylpyridinium chloride solution – 1 % aqueous thriethanolamine – water (7:5:5:1:7 by vol.). In this chromatographic conditions the capsaicin retention is about 0.53 (visualization by 2,6-dichlorochinon-4-chlorimide). Micellar mobile phase allow to separate of capsaicin from other components of plant materials, and lead to capsaicin assay. Micellar TLC method was validated according to follow parameters: selectivity, linearity, accuracy, precision and robustness. Method is express, economical and ecological, and can be as alternative for column liquid chromatography for capsaicin assay in plant material and extract from red hot pepper.

Keywords: capsaicin, red pepper, micellar thin-layer chromatography, validation.


UDC 615.225.2+615.453.64

Yuryeva O.O.

Public Joint Stock Company «Farmak»

Research range of excipients and determine the type of technology in the manufacture of solid combination dosage form of valsartan

The article focuses on а marketing research of valsartan’s drugs on the pharmaceutical market of Ukraine. Analyzed valsartan’s drugs range by content of active pharmaceutical ingredients, dosage form, novelty, countries and manufacturers. In Ukraine there are registered 96 names of valsartan in the form of tablets, film coated shell, containing from 40 mg to 320 mg of the active pharmaceutical ingredient. Mono-drugs account for 38.5 % and combined (with hydrochlorothiazide and amlodipine besylate) — 61.5 %. Foreign manufacturers presented most solid drugs of valsartan. Characterized range of excipients used in solid dosage forms of valsartan. It was established that the tablets excipients include the following groups: fillers, disintegrants, binders, lubricants, components of film coating system. It was established that the composition of valsartan tablets often include microcrystalline cellulose, povidone, croscarmellose sodium, magnesium stearate, colloidal silicon dioxide, film system based on hydroxypropylmethylcellulose. The results of the statistical analysis of the preparation of valsartan suggests possible tablet manufacturing technology — a method of wet granulation or compaction.

Keywords: valsartan, marketing research, excipients.


UDC 615.456.+658.562.012.7

Меrkulova Yu.V., Chaika Л.О., Belyakova E.S.

State Enterprise «Ukrainian Scientific Pharmacopoeial Center for Quality of Medicines»

Relevance of quality control of drugs in terms of «Depressor substances». Generalizing analysis of tests

What is the relevance of the quality control of drugs that contain ‘depressor substances’? The following is a summary of the test analysis; It is a requirement of the regulatory documents that any adverse effects of antibacterial drugs and biological medical product that is isolated from animal sources be tested against the normal permissible standards. This has been done by carrying out intravenous injections of cats with drugs from microbial (kanamycin, lincomycin, streptomycin, gentamicin), semi-synthetic (doxorubicin) and animal (heparin) sources. We carried out a comprehensive analysis of experimental data on any unwanted depressant effects of antibacterial pharmaceuticals and it was determined that the vasoactive substance antihyperitensive response does not exceed the appropriate accepted standard. The data suggests a number of undesirable impurities of histamine-like substances in the tested drugs and this would justify that these be biologically controlled in an appropriate test.

Keywords: depressor substance, histamine, vasodilatations, cats, biological methods of control.


UDC 616.127-005.8-036.6-037

Kopytsya M.P., Tytarenko N.V., Hyleva Y.V., Rodionova Y.V., Vyshnevskaya I.R., Petenyova L.L., Gonchar O.V.

National Therapy Institute of L.T. Malaya NAMS of Ukraine, Kharkiv

Prediction of death due 6 months in patients with acute Q-positive myocardial infarction

It is shown that there is an increased interest in the world in optimizing the scales of risk stratification of patients with acute myocardial infarction (AMI) due to the high mortality in this disease. The aim of this study was to define the utility of the measurement N-terminal pro-brain natriuretic peptide (NT-proBNP) and other clinical and biochemical markers to predict death at 6 months in patients with AMI. We included 151 consecutive patients admitted in hospital for acute Q-positive myocardial infarction. The parameters in patients with and without adverse events were taken for analysis: age, levels of creatinine and NT-proBNP, localization of infarction. Curves of sensitivity and specificity were used based on the method of ROC-analysis and cut-off values were chosen for each variable. Ball scoring was performed for each parameter regard to the cut-off value and a scale for calculating the summarized diagnostic coefficient by the method of Gubler was offered. We had performed a model of risk stratification of patients with acute myocardial infarction within 6 months, taking into account the patient’s age, the levels of creatinine and NT-proBNP, and localization of myocardial infarction. The sensitivity of the proposed model in predicting lethal result in patients with acute myocardial infarction was 81 %, specificity — 85 %, the area under the curve — 0.893.

Keywords: myocardial infarction, prediction of death, NTproBNP.


UDC 615.076

Blazheyevskiy M.Ye., Koval’ska O.V.

National University of Pharmacy

Comparative characteristics of the analytical methods which are suitable for quantitative determination decamethoxinе

The review article is devoted to the choice of the analytical methods of the quantitative determination decametoxine in during biomedical research. In comparative aspect discussed advantages and disadvantages of the known analytical methods of quantification of quaternary ammonium compounds (QAC), in particular decamethoxinum in medicines and biological fluids. In particular, critically has been analyzed of the possibility of use of the known methods of isolation the QAC from the objects with their subsequent determination of chromatographic techniques. A detailed analysis of the properties of QAC as a cholinesterase inhibitor and shows the prospect of application describing the kinetics of the newly-spectrophotometric method for direct measurement of cholinesterase activity to quantify the decametoxine as an inhibitor of biochemical reactions in biological fluids (intestinal fluid infusion and/or blood plasma).

Keywords: quaternary ammonium compounds, decamethoxine, the biological fluid, determination, the biochemical method


UDC 615.21]:342.951:615

Shapovalov V.V., Komar L.О., Shapovalova V.О., Shapovalov V.V.

Kharkiv medical academy of postgraduate education Department of healthcare of Kharkiv state regional administration

Study of the particularities of the circulation of combined OTC medicines with calming action

In modern terms the irrational use of combined medicines with controlled active pharmaceutical ingredients of different legal and classification groups continues to grow steadily. Aim of the research was to study the characteristics of circulation on the pharmaceutical market of Ukraine of combined OTC medicines with calming action. The study found that circulation on the pharmaceutical market of Ukraine are mainly based medicines with valerian drops as domestic production. In study the control regime of combined OTC medicines found that for clinical and pharmacological basis of most drugs — 91.7 % are hypnotic and sedatives (N05CM50); for the classification and legal grounds all medicines related to the total group, and the nomenclature and legal grounds – to the OTC. This mode control combined OTC medicines with calming action indicates their availability to patients. However, despite the free access to combined OTC medicines, they should be tailored to suit their application, including combined OTC drugs with calming action may potentiate the action of sedatives, sleeping pills, antispasmodic, antihypertensive medications central action, tranquilizers, antipsychotics, alcohol; can affect the rate of reaction. Alcohol-containing medicines zelenin drops, valokormid and neo-passit not be used for children under 3 years old, pregnant women, women who are being treated for alcohol dependence.

Keywords: pharmaceutical law, pharmaceutical market, circulation, combined OTC medicines, protocols of the pharmacist, forensic pharmacy