pmedpharmФармация и фармакологияPharmacy & Pharmacology2307-92662413-2241Pyatigorsk Medical and Pharmaceutical Institute - branch of Volgograd State Medical Univer10.19163/2307-9266-2022-10-4-331-342pmedpharm-1162Research ArticleФАРМАКОЛОГИЯ И КЛИНИЧЕСКАЯ ФАРМАКОЛОГИЯPHARMACOLOGY AND CLINICAL PHARMACOLOGYАДАПТАЦИЯ МЕТОДА «ВЫСУШЕННОЙ КАПЛИ КРОВИ» ДЛЯ ПРОВЕДЕНИЯ ТЕРАПЕВТИЧЕСКОГО ЛЕКАРСТВЕННОГО МОНИТОРИНГАADAPTATION OF “DRIED BLOOD DROP” METHOD FOR THERAPEUTIC DRUG MONITORINGhttps://orcid.org/0000-0002-0258-4092ПетровВ. И.PetrovV. I.

доктор медицинских наук, профессор, академик РАН, заведующий кафедрой клинической фармакологии и интенсивной терапии ФГБОУ ВО ВолгГМУ Минздрава России; директор НЦИЛС ВолгГМУ, главный внештатный специалист – клинический фармаколог Министерства здравоохранения РФ, заслуженный деятель науки РФ, заслуженный врач РФ

400131, Россия, г. Волгоград, пл. Павших Борцов, д. 1

400087, Россия, г. Волгоград, ул. Новороссийская, д. 39

Doctor of Sciences (Medicine), Professor, Academician of the Russian Academy of Sciences; Head of the Department of Clinical Pharmacology and Intensive Care, Volgograd State Medical University; director of Scientific Centre of Innovative Medicines with Pilot Production, Volgograd State Medical University; Chief freelance specialist – a clinical pharmacologist of the Ministry of Health of the Russian Federation; Honored Scientist of the Russian Federation; Honored Doctor of the Russian Federation

 

1, Pavshikh Bortsov Sq., Volgograd, Russia, 400131

39, Novorossiyskaya Str., Volgograd, Russia, 400087

brain@sprintnet.ruhttps://orcid.org/0000-0002-9384-4338АникеевИ. С.AnikeevI. S.

аспирант кафедры клинической фармакологии и интенсивной терапии ФГБОУ ВО ВолгГМУ Минздрава России; заведующий лабораторией фармакокинетики НЦИЛС ФГБОУ ВО ВолгГМУ Минздрава России

400131, Россия, г. Волгоград, пл. Павших Борцов, д. 1

400087, Россия, г. Волгоград, ул. Новороссийская, д. 39

post-graduate student, Department of Clinical Pharmacology and Intensive Care, Volgograd State Medical University; Head of the Laboratory of Pharmacokinetics, Scientific Center of Innovative Medicines with Pilot Production, Volgograd State Medical University

 

1, Pavshikh Bortsov Sq., Volgograd, Russia, 400131

39, Novorossiyskaya Str., Volgograd, Russia, 400087

Anikeev.iv@gmail.comhttps://orcid.org/0000-0001-6758-4686ЗаячниковаТ. Е.ZayachnikovaT. E.

кандидат медицинских наук, доцент, профессор кафедры педиатрии и неонатологии Института непрерывного медицинского и фармацевтического образования 

400131, Россия, г. Волгоград, пл. Павших Борцов, д. 1

Candidate of Sciences (Medicine), Associate Professor, Professor of the Department of Pediatrics and Neonatology, Institute of Continuous Medical and Pharmaceutical Education, Volgograd State Medical University

1, Pavshikh Bortsov Sq., Volgograd, Russia, 400131

guz5deti@mail.ruhttps://orcid.org/0000-0002-6997-1601СтрыгинА. В.StryginA. V.

кандидат медицинских наук, доцент, заведующий кафедрой фундаментальной медицины и биологии ФГБОУ ВО ВолгГМУ Минздрава России; заместитель директора НЦИЛС ФГБОУ ВО ВолгГМУ Минздрава России; заведующий лабораторией геномных и протеомных исследований ГБУ ВМНЦ

400131, Россия, г. Волгоград, пл. Павших Борцов, д. 1

400087, Россия, г. Волгоград, ул. Новороссийская, д. 39

Candidate of Sciences (Medicine), Associate Professor, Head of the Department of Fundamental Medicine and Biology, Volgograd State Medical University; Deputy Director of Scientific Center of Innovative Medicines with Pilot Production, Volgograd State Medical University; Head of the Laboratory of Genomic and Proteomic Research, Volgograd Medical Research Center

 

1, Pavshikh Bortsov Sq., Volgograd, Russia, 400131

39, Novorossiyskaya Str., Volgograd, Russia, 400087

 

 

drumsav@mail.ruhttps://orcid.org/0000-0003-3324-3351ДоценкоА. М.DotsenkoA. M.

ассистент кафедры фундаментальной медицины и биологии ФГБОУ ВО ВолгГМУ Минздрава России; младший научный сотрудник лаборатории геномных и протеомных исследований ГБУ ВМНЦ

400131, Россия, г. Волгоград, пл. Павших Борцов, д. 1

Assistant of the Department of Fundamental Medicine and Biology, Volgograd State Medical University; Junior Researcher, Laboratory of Genomic and Proteomic Research, Volgograd Medical Research Center

1, Pavshikh Bortsov Sq., Volgograd, Russia, 400131

 

ev8278@mail.ruФедеральное государственное бюджетное образовательное учреждение высшего образования «Волгоградский государственный медицинский университет» Министерства здравоохранения Российской Федерации Центр инновационных лекарственных средств с опытно-промышленным производством федерального государственного бюджетного образовательного учреждения высшего образования «Волгоградский государственный медицинский университет»РоссияVolgograd State Medical University Institute for Continuing Medical and Pharmaceutical Education, Volgograd State Medical UniversityRussian FederationИнститут непрерывного медицинского и фармацевтического образования федерального государственного бюджетного образовательного учреждения высшего образования «Волгоградский государственный медицинский университет» Министерства здравоохранения Российской ФедерацииРоссияInstitute for Continuing Medical and Pharmaceutical Education, Volgograd State Medical UniversityRussian FederationФедеральное государственное бюджетное образовательное учреждение высшего образования «Волгоградский государственный медицинский университет» Министерства здравоохранения Российской Федерации 2 Центр инновационных лекарственных средств с опытно-промышленным производством федерального государственного бюджетного образовательного учреждения высшего образования «Волгоградский государственный медицинский университет» Министерства здравоохранения Российской Федерации Государственное бюджетное учреждение «Волгоградский медицинский научный центр»РоссияVolgograd State Medical University Scientific Center of Innovative Medicines with Pilot Production, Volgograd State Medical University Volgograd Medical Research CenterRussian FederationФедеральное государственное бюджетное образовательное учреждение высшего образования «Волгоградский государственный медицинский университет» Министерства здравоохранения Российской Федерации Государственное бюджетное учреждение «Волгоградский медицинский научный центр»РоссияVolgograd State Medical University Volgograd Medical Research CenterRussian Federation202229102022104331342Copyright © Петров В.И., Аникеев И.С., Заячникова Т.Е., Стрыгин А.В., Доценко А.М., 20222022Петров В.И., Аникеев И.С., Заячникова Т.Е., Стрыгин А.В., Доценко А.М.Petrov V.I., Anikeev I.S., Zayachnikova T.E., Strygin A.V., Dotsenko A.M.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.pharmpharm.ru/jour/article/view/1162

Для контроля концентрации лекарственных препаратов, обладающих узким терапевтическим диапазоном, и проведения эффективных и безопасных методов лечения проводится терапевтический лекарственный мониторинг (ТЛМ). Однако на сегодняшний день проведение ТЛМ связано с различными затруднениями, для решения которых разрабатываются более удобные и менее инвазивные методы сбора биологического материла.

Цель

Цель. Разработать протоколы взятия и хранения образцов «высушенной капли крови» (Dried Blood Spot, DBS), а также протоколы валидации методов количественного определения лекарственных препаратов в цельной крови с использованием данной технологии для последующего проведения терапевтического лекарственного мониторинга.

Материалы и методы

Материалы и методы. Для детального анализа метода «высушенной капли крови» и выявления характерных особенностей взятия и хранения биообразцов, был проведен сбор и анализ научной литературы за последние 10 лет. Поиск литературных материалов проводился с помощью открытых и доступных источников, размещенных в научных библиотеках учреждений, в электронных базах данных и поисковых системах: Elibrary, PubMed, Scopus, КиберЛенинка, Medline, ScienceDirect, Web of Science, Google Scholar. Подготовили первичные протоколы взятия, хранения и анализа образцов «высушенной капли крови». На стадиях отбора и хранения проводили апробацию и оптимизацию разработанных протоколов для получения образцов надлежащего качества. Методом высокоэффективной жидкостной хроматографии с масс-спектрометрической детекцией (ВЭЖХ-МС/МС) с использованием в качестве пробоподготовки «высушенную каплю крови», оптимизировали протоколы валидации лекарственных препаратов для обеспечения достижения приемлемых валидационных характеристик и проведения последующего ТЛМ.

Результаты

Результаты. Выявлены особенности сбора, хранения и анализа образцов «высушенной капли крови». Определены такие характеристики, как: эффект объёма капли, эффект гематокрита, однородность капли, которые могут оказывать влияние на результаты количественного ВЭЖХ-МС/МС анализа. Для успешного использования новой методики нами были разработаны надлежащие протоколы взятия образцов «высушенной капли крови» из пальца руки взрослых пациентов и из пятки новорожденных детей, а также протоколы валидации методов количественного определения лекарственных препаратов из данных образцов.

Заключение

Заключение. Применение метода «высушенной капли крови» с использованием новых разработанных протоколов взятия, хранения и анализа биологических образцов снимает существующие ограничения при проведении ТЛМ, а также в последствии может стать перспективным методом для проведения доклинических и клинических исследований. 

To control the concentration of drugs with a narrow therapeutic range, and to conduct effective and safe treatments, Therapeutic Drug Monitoring (TDM) is carried out. However, to date, the implementation of TDM is associated with various difficulties, for the solution of which more convenient and less invasive methods for collecting biological material are being developed.

The aim of the study was to develop protocols for the collection and storage of “dried blood spot” (DBS) samples, as well as protocols for the validation methods for the quantitative determination of drugs in whole blood, using this technology for subsequent therapeutic drug monitoring.

Materials and methods

Materials and methods. To analyze a “dried blood spot” method in detail and to identify the characteristic features of taking and storing biosamples, a collection and analysis of scientific literature over the past 10 years has been conducted. The search for literature materials has been carried out from open and accessible sources located in the scientific libraries of institutions, in electronic databases and search engines: Elibrary, PubMed, Scopus, Cyberleninka, Medline, ScienceDirect, Web of Science, Google Scholar. Primary protocols for taking, storing and analyzing samples of the “dried blood drop” have been prepared. To obtain the adequate quality samples, the developed protocols have been tested and optimized at the stages of selection and storage. By high-performance liquid chromatography with mass spectrometric detection (HPLC-MS/MS), using a “dried blood drop” as a sample preparation, drug validation protocols have been optimized to ensure that acceptable validation characteristics were achieved, and subsequent Therapeutic Drug Monitoring was performed.

Results

Results. The features of the collection, storage and analysis of the “dried blood spot” samples have been revealed. Such characteristics as a spot volume effect, a hematocrit effect, a droplet uniformity, which can affect the results of a quantitative HPLC-MS/MS analysis, have been determined. For a successful use of the new methods, appropriate protocols for taking samples of “dried blood spot” from the finger of adult patients and from the heel of newborns, as well as protocols for validating methods for the quantitative determination of drugs from these samples, have been developed.

Conclusion

Conclusion. The application of the “dried blood spot” method using newly developed protocols for taking, storing and analyzing biological samples, relieves the existing constraints in conducting TDM, and can later become a promising method for conducting preclinical and clinical studies.

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The authors declare that there are no conflicts of interest present.