Представлены результаты разработки ВЭЖХ-методики количественного определения меропенема в плазме крови человека для терапевтического лекарственного мониторинга в условиях стационара. Детектирование осуществляли спектрофотометрически при 298 нм, время хроматографирования составило 12 мин. Методика валидирована по основным параметрам, при этом линейность наблюдалась в широком диапазоне концентраций (от 0,2 до 150 мкг/мл), а нижний предел количественного определения составил 0,2 мкг/мл. Коэффициент корреляции градуировочной кривой составил 0,9998. Нижний предел количественного определения на уровне 0,2 мкг/мл обеспечивает необходимую чувствительность методики. Показана применимость разработанной методики для оперативного контроля содержания меропенема в плазме крови пациентов, что позволяет индивидуализировать дозы препарата и повысить эффективность и рациональность антибактериальной терапии.

The development of an HPLC method for quantitative determination of meropenem in human blood plasma for therapeutic drug monitoring in clinics is reported. Spectrophotometric detection was made at 298 nm. The chromatography time was 12 min. The method was validated for the basic parameters and was linear over a wide concentration range (from 0.2 to 150 ìg/mL). The lower limit of quantitation was 0.2 ìg/mL, which provided the required method sensitivity. The correlation coefficient of the calibration curve was 0.9998. The developed method was shown to be applicable for real-time monitoring of the meropenem content in patient blood plasma, which allowed the dose to be personalized and the efficacy and rationality of the antibacterial therapy to be increased.

Introduction. N-nitrosamine compounds are potent genotoxic agents in animal species and some are classified as probable human carcinogens. This group of genotoxic impurities was found in drugs such as angiotensin II receptor blockers, histamine H1 receptor antagonists, and synthetic antidiabetic drugs. This discovery caused a flurry of alarm in the global pharmaceutical industry and resulted in a series of international investigations trying to determine root causes of nitrosamine formation in medicinal products and to find ways to minimize risks associated with nitrosamine contamination.Text. This paper provides an overview of the current state of the problem. It summarises the main pathways of N-nitrosamine formation in medicinal products at the stages from synthesis of active pharmaceutical ingredients to storage of finished pharmaceutical products. The paper describes the main mechanism responsible for the toxic effect of this group of impurities in human body. It also describes methods of extraction and analysis of N-nitrosamines found in medicinal products. It was demonstrated that high-performance liquid chromatography and gas chromatography-mass spectrometry are a golden standard for the detection of these contaminants. The paper also touches upon the main principles of setting limits for nitrosamine impurities in medicinal products.Conclusion. The data presented give a picture of the root causes of N-nitrosamine formation in medicinal products, as well as current detection and control methods used worldwide. Meanwhile, the paper raises a key issue about the need to develop Russian standards that would control the purity of medicinal products in terms of N-nitrosamine impurities. For that end, it will be necessary to draw on the experience of the leading USA and EU regulatory authorities.

The current state of quality standards for radiopharmaceuticals (RPs) for positron-emission tomography (PET) is assessed considering primarily national and global requirements for pharmacopoeial practice. The need to develop both general pharmacopoeial standards for RPs for PET and specific monographs for separate pharmaceuticals is established. Common approaches to standardization of each quality indicator are proposed considering known features of PET RPs using dosage forms for parenteral administration as examples.

General approaches to the elaboration of pharmacopoeial quality standards for medicinal products that are based on good pharmacopoeial practice (GPhP) rules of domestic and leading foreign pharmacopoeias are presented.

The current classification of impurities in chemical and mineral drug substances is presented. General approaches to standardization of chemical and mineral drug substances according to the Purity section are given depending on their origin and production technology and considering requirements of international and domestic pharmacopoeial practice

A capillary electrophoresis technique for quantitative determination of phenibut in microcapsules was developed and validated. Rather high efficiencies (~200,000 theoretical plates) and the required resolution (Rs ≥ 1.5) were attained using sodium tetraborate decahydrate solution (10 mM) at pH 9.2 as the supporting electrolyte. Validation of the technique showed that it was specific and complied with requirements of the SP XIIIth Ed. with respect to analytical range and linearity.

Методом капиллярного электрофореза проведена разработка и валидация методики количественного определения фенибута в микрокапсулах. Показано, что при использовании в качестве ведущего электролита 10 мМ раствора натрия тетраборнокислого 10-водного с рН 9,2 достигаются достаточно высокие параметры эффективности (около 200 000 т.т.) и необходимое разрешение (Rs ≥ 1,5). Проведенная валидационная оценка разработанной методики показала, что методика является специфичной, а по показателям аналитическая область и линейность соответствует требованиям ГФ XIII изд.

Приведена современная классификация примесей в фармацевтических субстанциях химического и минерального происхождения. Представлены общие подходы к стандартизации фармацевтических субстанций химического и минерального происхождения по разделу «Чистота» в зависимости от их происхождения и технологии получения, а также с учётом требований мировой и отечественной фармакопейной практики.

Представлены общие подходы к разработке фармакопейных стандартов к качеству лекарственных препаратов на основании требований надлежащей фармакопейной практики (GPhP) отечественной и ведущих зарубежных фармакопей.

A micellar electrokinetic chromatographic method for quantitative determination of sesquiterpene lactones (costunolide and dehydrocostuslactone) from Laurus nobilis leaves was developed. It was shown that urea had to be added to the leading electrolyte in order to increase the analysis selectivity. The developed method was used to establish the costunolide and dehydrocostuslactone contents in various leaf samples as 0.5757 and 0.0399%, respectively, calculated per absolute dry raw material. The main validation characteristics of the developed method were also determined.

В настоящей статье обсуждаются результаты исследования фенольных соединений листьев скумпии кожевенной (Cotinus coggygria Scop.) методом ВЭЖХ. Высушенные образцы сырья были заготовлены в 2013 году в фазу цветения растения на юго-восточном склоне горы Машук в городе Пятигорске Ставропольского края. Исследование проведено в двух условиях: без гидролиза сырья и после кислотного гидролиза. Определено содержание 5 фенольных соединений, среди которых доминирующими являются гиперозид, рутин и феруловая кислота, а также кверцетин и кемпферол в незначительных количествах. В извлечении, полученном после проведения кислотного гидролиза, установлено значительное повышение содержания кверцетина и кемпферола, что свидетельствует о значительном содержании в сырье их производных (гликозиды, сложные эфиры). Использование указанного подхода может быть использовано для оценки качества сырья скумпии кожевенной.

Working out and further validation of the method of quantitative identification of dimebon in soft dosage forms were the purpose of the study. We used a method of spectrophotometry. For the first time we have developed the method of quantitative identification of dimebon in soft dosage forms by using spectrophotometry with a wavelength 270±2 nm. We have studied validation characteristics of the developed method, linearity, precision, and correctness.

We have developed a methodology of quantitative determination of sesquiterpenic lactones (costunolide and dehydrocostuslactone) in leaves of Laurus nobilis using reversed phase HPLC. We have determined optimal conditions for the substances under study extraction from active parts. Using the developed methods we have established that costunolide and dehydrocostuslactone content in Laurus nobilis samples in terms of absolutely dry active parts is 0.99 and 0.26% correspondingly.

Expansion of the range of modern effective and safe medicines can be reached with introduction in domestic medical practice of medicines natural and especially a phytogenesis. Among numerous problems of modern society one of the leading places occupies a psychoemotional stress. This emotional pressure is caused, as a rule, by the social conflicts. Among the sedatives which are available in the Russian pharmaceutical market of 70 % of a phytogenesis. However almost all of them have monostructure though in our opinion, complexity for preparations of such orientation of action, can be perspective. Data on identification and quantitative definition of a baicalin by method of a High performance liquid chromatography in spirit extraction of complex phytostructure are presented in article: grass of a Motherwort, roots of a Baikal skullcap, rhizomes with roots of a Jacob’s ladder received with use of filtrational extraction.

HPLC with mass spectroscopic detection was used to demonstrate that Forsythia intermedia (Forsythia x intermedia Zabel) flowers contain flavolignans: forsythin, phillygenin, isolariciresinol and, presumptively, its derivative hydroxyisolariciresinol, as well as the phenylethanoid glycoside forsythoside A. Forsythoside A was assayed by two methods - HPLC with spectrophotometric detection and capillary electrophoresis. Forsythoside A contents in flowers reached 1.5%.

The method of analysis suppositories containing cinnarizine and fenotropil was developed. The method of HPLC used for qualitative and quantitative analysis of cinnarizine and fenotropil. The study was conducted on a liquid chromatograph Stayer firm Aquilon (Russia USA Czech Republic) equipped with a column Luna C-18 of 4.6×150 mm (Phenomenex, USA), with a carbon content of 16%. It is established that the optimum is the gradient elution mode. Acetonitrile and formic acid 2% were used as the mobile phase. Detection was performed at a wavelength of 254 nm. Conducted a validation assessment of the proposed methodology criteria: linearity, accuracy, precision confirmed the possibility of its use for the quantitative determination of cinnarizine and fenotropil in suppositories.

The paper demonstrated the potential of HPLC and capillary electrophoresis when used for the analysis sesquiterpene lactones (costunolide and dehydrocostuslactone) in the leaves of laurel (Laurus nobilis L.). We found that both methods had yielded comparable results as to the content of costunolide and dehydrocostuslactone in all the samples of the studied raw materials.