Сравнительный Анализ Содержания Тяжелых Металлов, Алюминия И Мышьяка В Бурых Водорослях Различного Происхождения

Vedomosti Nauchnogo tsentra ekspertizy sredstv meditsinskogo pr

Кузьмина²,

Shvetsova³

et al. 2022

When the approach to quality control of herbal substances (HSs) and herbal medicinal products (HMPs) changed from determination of the total content of heavy metals by calorimetry to selective determination by spectrometric techniques, many manufacturers of such products failed to meet the new requirements in their registration dossiers. Test procedures submitted by manufacturers often need to be clarified, and validation protocols often lack data.The aim of the study was to provide recommendations to HS and HMP manufacturers on the choice of test methods, materials, reagents, methods of organic matrix mineralisation, and main validation parameters, as well as recommendations on validation of the procedure for elemental toxicants determination, and preparation of the “Heavy metals and arsenic” part of the regulatory submission.Materials and methods: the study included analysis and systematisation of scientific literature, requirements of the Russian and foreign pharmacopoeias, guidelines, manuals on instrumental methods of analysis, and first-hand experience in elemental analysis of various types of HSs and HMPs.Results: the authors formulated recommendations on the choice of sample mineralisation conditions for quantification of elemental impurities in biological products, and substantiated requirements for the reagents, materials, and equipment. The paper compares different methods of elemental analysis. It was demonstrated that the main mistakes made by manufacturers stem from disregard to the organic matrix effect on the measurement results and lack of agreement between the impurity concentration being determined and the range of the calibration curve used. The paper gives acceptance criteria for validation parameters of test procedures for heavy metals and arsenic determination in HSs and HMPs.Conclusions: it is not correct to use reference standards containing heavy metals as inorganic salts not bound to organic compounds, for HS and HMP analysis. The criteria given in the European Pharmacopoeia and the United State Pharmacopoeia can be used for a number of validation parameters, when they are not included in the Russian Pharmacopoeia.

Section: материалы и методыunclassified

Section: результаты и обсуждениеunclassified

Development and Validation of Procedures for Determination of Elemental Toxicants in Herbal Substances and Herbal Medicinal Products

Vedomosti Nauchnogo tsentra ekspertizy sredstv meditsinskogo pr

Кузьмина²,

Shvetsova³

et al. 2022

“…Следует отметить, что наиболее токсичными формами соединений мышьяка являются неорганические формы, которые в сотни раз более токсичны, чем органические [59]. Ранее считалось, что в морской биоте, несмотря на большое количество общего мышьяка, доля его неорганической формы крайне мала.…”

Section: Fig 2 Content Of Cadmium In the Herbal Medicinal Products unclassified

Comparative Analysis of Heavy Metal and Arsenic Content in Various Herbal Dosage Forms Marketed in Russia

Vedomosti Nauchnogo tsentra ekspertizy sredstv meditsinskogo pr

Кузьмина²,

Shvetsova³

et al. 2020

The inclusion of requirements for independent determination of arsenic, cadmium, mercury, and lead, and the current sample preparation techniques into the State Pharmacopoeia of the Russian Federation (Ph. Rus.) requires the revision of the existing limits for elemental toxicants in herbal substances and herbal medicinal products produced from them.The aim of the study was to analyse the data on elemental toxicant content obtained during quality control of herbal substances (herbs, medicinal herb mixtures, extracts, and tinctures) using current test methods and sample preparation techniques, and to compare the obtained results with the Russian and foreign scientific and specialist literature.Materials and methods: the internal data on the content of critical heavy metals and arsenic in different dosage forms of herbal medicinal products, which were obtained by inductively coupled plasma mass spectrometry after sample preparation by decomposition in closed vessels, were compared with literature data. Results: it was demonstrated that the content of lead, cadmium, and mercury in all the test samples did not exceed the Ph. Rus. limits and was consistent with the analysed literature. The arsenic content in some herbal medicinal products was higher than the established Ph. Rus. limits, but complied with the less stringent Ph. Eur. and USP requirements for herbal substances. The authors investigated the link between the content of elemental toxicants and the place of collection and the part of the plant being tested. It was shown that different types of medicinal plants had a tendency to accumulate particular elements. The authors determined the content of the elements to be controlled in extracts and tinctures. The differences in the Russian and foreign requirements for the content of elemental toxicants may be attributed to the method of obtaining experimental data that form the basis for the setting of limits.Conclusions: the results of the study confirm the validity of the existing limits for elemental toxicants in herbal medicinal products. The authors demonstrated the need to revise the existing limits for arsenic in herbal medicinal products.

“…В настоящее время в зарубежной нормативной практике существует несколько принципиально различных подходов к нормированию содержания мышьяка в бурых водорослях. Проведенные нами исследования [7] показали необходимость изменения существующих российских норм, касающихся содержания мышьяка применительно к бурым водорослям как лекарственным растительным препа-ратам, так как существующие нормы не позволяют в полной мере провести оценку безопасности их использования.…”

Section: обзоры / Reviewsunclassified

“…IX изд. 7 ). В существующем проекте фармакопеи ЕАЭС указаны общие нормы по содержанию элементных токсикантов для всего растительного сырья, и не предусмотрена возможность введения индивидуальных норм для отдельных видов ЛРП 8 , общее содержание мышьяка лимитировано на уровне 0,5 мг/кг.…”

Section: обзоры / Reviewsunclassified

Problems of Establishing Limits for Arsenic Content in Brown Algae and Brown Algae-Containing Medicinal Products

Vedomosti Nauchnogo tsentra ekspertizy sredstv meditsinskogo pr

Ерина²,

Лисман³

et al. 2019

Algae tend to accumulate elemental toxic substances in high concentrations. Algae are widely used in the food and pharmaceutical industries, and this dictates the need to establish limits for the content of toxic substances that they may contain. The aim of the study was to analyse the requirements of the Russian and foreign pharmacopoeias and other regulatory documents concerning the limits for the content of arsenic in brown algae. The paper presents the results of analysis of monographs from the State Pharmacopoeia of the Russian Federation, XIII and XIV editions, draft version of the Pharmacopoeia of the Eurasian Economic Union, United States Pharmacopoeia, Japanese Pharmacopoeia, European Pharmacopoeia, and Ayurvedic Pharmacopoeia of India containing limits for the content of arsenic in herbal medicinal products (HMPs). In addition, the authors analysed Russian, international and foreign food industry and dietary supplements regulations, as well as scientific publications on arsenic content in brown algae. They also considered the nomenclature of arsenic compounds to be determined and controlled in medicinal products, highlighted the main approaches to and identified global trends in establishing the limits for their content in HMPs. The paper summarises specific aspects of inorganic arsenic compounds accumulation by brown algae. It was demonstrated that the majority of foreign pharmacopoeias either have specific norms for arsenic content in brown algae, which differ from the norms for HMPs, or have general norms that take into account different toxicity levels of organic and inorganic arsenic compounds. There is a tendency to control the content of elemental toxic substances based on their maximum allowable daily intake. The paper substantiates the need for separate determination of toxic inorganic arsenic compounds and potentially toxic methyl arsonate and dimethyl arsinate in HMPs.