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<article article-type="research-article" dtd-version="1.3" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xml:lang="ru"><front><journal-meta><journal-id journal-id-type="publisher-id">pmedpharm</journal-id><journal-title-group><journal-title xml:lang="ru">Фармация и фармакология</journal-title><trans-title-group xml:lang="en"><trans-title>Pharmacy &amp; Pharmacology</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">2307-9266</issn><issn pub-type="epub">2413-2241</issn><publisher><publisher-name>Pyatigorsk Medical and Pharmaceutical Institute - branch of Volgograd State Medical Univer</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.19163/2307-9266-2023-11-4-280-290</article-id><article-id custom-type="elpub" pub-id-type="custom">pmedpharm-1381</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="ru"><subject>ОРИГИНАЛЬНАЯ СТАТЬЯ</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>RESEARCH ARTICLE</subject></subj-group></article-categories><title-group><article-title>Оптимизация терапевтического лекарственного мониторинга ванкомицина у новорожденных с применением метода «высушенной капли крови»</article-title><trans-title-group xml:lang="en"><trans-title>Optimization of therapeutic drug monitoring of vancomycin in newborns using “Dried Blood Spot” method</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-0258-4092</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Петров</surname><given-names>В. И.</given-names></name><name name-style="western" xml:lang="en"><surname>Petrov</surname><given-names>V. I.</given-names></name></name-alternatives><bio xml:lang="ru"><p>доктор медицинских наук, профессор, академик РАН, заведующий кафедрой клинической фармакологии и интенсивной терапии ФГБОУ ВО ВолгГМУ Минздрава России; главный внештатный специалист – клинический фармаколог Министерства здравоохранения РФ, заслуженный деятель науки РФ, заслуженный врач РФ.</p><p>400131, Россия, г. Волгоград, пл. Павших Борцов, д. 1</p></bio><bio xml:lang="en"><p>Doctor of Sciences (Medicine), Professor, Academician of the Russian Academy of Sciences; Head of the Department of Clinical Pharmacology and Intensive Care of 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. </p><p>1, Pavshih Borcov Sq., Volgograd, Russia, 400131</p></bio><email xlink:type="simple">brain@sprintnet.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-9384-4338</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Аникеев</surname><given-names>И. С.</given-names></name><name name-style="western" xml:lang="en"><surname>Anikeev</surname><given-names>I. S.</given-names></name></name-alternatives><bio xml:lang="ru"><p>ассистент кафедры фундаментальной медицины и биологии ФГБОУ ВО ВолгГМУ Минздрава России; заведующий лабораторией фармакокинетики НЦИЛС ВолгГМУ Минздрава России.</p><p>400131, Россия, г. Волгоград, пл. Павших Борцов, д. 1.</p><p>400087, Россия, г. Волгоград, ул. Новороссийская, д. 39.</p></bio><bio xml:lang="en"><p>assistant of the Department of Fundamental Medicine and Biology, Volgograd State Medical University; Head of the Laboratory of Pharmacokinetics of Scientific Center of Innovative Medicines with Pilot Production of Volgograd State Medical University.</p><p>1, Pavshih Borcov Sq., Volgograd, Russia, 400131.</p><p>39, Novorossiyskaya Str., Volgograd, Russia, 400087.</p></bio><email xlink:type="simple">anikeivan@yandex.ru</email><xref ref-type="aff" rid="aff-2"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-6758-4686</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Заячникова</surname><given-names>Т. Е.</given-names></name><name name-style="western" xml:lang="en"><surname>Zayachnikova</surname><given-names>T. E.</given-names></name></name-alternatives><bio xml:lang="ru"><p>кандидат медицинских наук, доцент, профессор кафедры педиатрии и неонатологии Института непрерывного медицинского и фармацевтического образования ФГБОУ ВО ВолгГМУ Минздрава России.</p><p>400131, Россия, г. Волгоград, пл. Павших Борцов, д. 1</p></bio><bio xml:lang="en"><p>Candidate of Sciences (Medicine), Associate Professor, Professor of the Department of Pediatrics and Neonatology, Institute of Continuing Medical and Pharmaceutical Education of Volgograd State Medical University. </p><p>1, Pavshih Borcov Sq., Volgograd, Russia, 400131</p></bio><email xlink:type="simple">guz5deti@mail.ru</email><xref ref-type="aff" rid="aff-3"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-6997-1601</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Стрыгин</surname><given-names>А. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Strygin</surname><given-names>A. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>кандидат медицинских наук, доцент, заведующий кафедрой фундаментальной медицины и биологии ФГБОУ ВО ВолгГМУ Минздрава России; заместитель директора НЦИЛС ФГБОУ ВО ВолгГМУ Минздрава России.</p><p>400087, Россия, г. Волгоград, ул. Новороссийская, д. 39.</p><p>400131, Россия, г. Волгоград, пл. Павших Борцов, д. 1</p></bio><bio xml:lang="en"><p>Candidate of Sciences (Medicine), Associate Professor, Head of the Department of Fundamental Medicine and Biology of Volgograd State Medical University; Deputy Director of Scientific Center of Innovative Medicines with Pilot Production of Volgograd State Medical University. </p><p>1, Pavshih Borcov Sq., Volgograd, Russia, 400131.</p><p>39, Novorossiyskaya Str., Volgograd, Russia, 400087.</p></bio><email xlink:type="simple">drumsav@mail.ru</email><xref ref-type="aff" rid="aff-2"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-1116-3425</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Куркин</surname><given-names>Д. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Kurkin</surname><given-names>D. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>доктор фармацевтических наук, доцент, профессор кафедры клинической фармакологии и интенсивной терапии ФГБОУ ВО ВолгГМУ Минздрава России; старший научный сотрудник лаборатории фармакологии сердечно-сосудистых систем НЦИЛС ФГБОУ ВО ВолгГМУ Минздрава России. </p><p>400087, Россия, г. Волгоград, ул. Новороссийская, д. 39.</p><p>400131, Россия, г. Волгоград, пл. Павших Борцов, д. 1.</p></bio><bio xml:lang="en"><p>Doctor of Sciences (Pharmacy), Associate Professor, Professor of the Department of Clinical Pharmacology and Intensive Care of Volgograd State Medical University; Senior Researcher, Laboratory of Pharmacology of Cardiovascular Systems of Scientific Center of Innovative Medicines with Pilot Production of Volgograd State Medical University. </p><p>1, Pavshih Borcov Sq., Volgograd, Russia, 400131.</p><p>39, Novorossiyskaya Str., Volgograd, Russia, 400087.</p></bio><email xlink:type="simple">strannik986@mail.ru</email><xref ref-type="aff" rid="aff-2"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-3324-3351</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Казьмина</surname><given-names>Ю. С.</given-names></name><name name-style="western" xml:lang="en"><surname>Kazmina</surname><given-names>Yu. S.</given-names></name></name-alternatives><bio xml:lang="ru"><p>ассистент кафедры фундаментальной медицины и биологии ФГБОУ ВО ВолгГМУ Минздрава России. </p><p>400131, Россия, г. Волгоград, пл. Павших Борцов, д. 1</p></bio><bio xml:lang="en"><p>assistant at the Department of Fundamental Medicine and Biology of the Volgograd State Medical University.</p><p>1, Pavshih Borcov Sq., Volgograd, Russia, 400131.</p></bio><email xlink:type="simple">ev8278@mail.ru</email><xref ref-type="aff" rid="aff-1"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>Федеральное государственное бюджетное образовательное учреждение высшего образования «Волгоградский государственный медицинский университет» Министерства здравоохранения Российской Федерации</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Volgograd State Medical University</institution><country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-2"><aff xml:lang="ru"><institution>Федеральное государственное бюджетное образовательное учреждение высшего образования «Волгоградский государственный медицинский университет» Министерства здравоохранения Российской Федерации.&#13;
Научный центр инновационных лекарственных средств с опытно-промышленным производством федерального государственного бюджетного образовательного учреждения высшего образования «Волгоградский государственный медицинский университет» Министерства здравоохранения Российской Федерации.</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Volgograd State Medical University.&#13;
Center for Innovative Medicines with Pilot Industrial Production of Volgograd State Medical University.</institution><country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-3"><aff xml:lang="ru"><institution>Институт непрерывного медицинского и фармацевтического образования федерального государственного бюджетного образовательного учреждения высшего образования «Волгоградский государственный медицинский университет» Министерства здравоохранения Российской Федерации</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Institute of Continuing Medical and Pharmaceutical Education of Volgograd State Medical University</institution><country>Russian Federation</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2023</year></pub-date><pub-date pub-type="epub"><day>09</day><month>01</month><year>2024</year></pub-date><volume>11</volume><issue>4</issue><fpage>280</fpage><lpage>290</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Петров В.И., Аникеев И.С., Заячникова Т.Е., Стрыгин А.В., Куркин Д.В., Казьмина Ю.С., 2024</copyright-statement><copyright-year>2024</copyright-year><copyright-holder xml:lang="ru">Петров В.И., Аникеев И.С., Заячникова Т.Е., Стрыгин А.В., Куркин Д.В., Казьмина Ю.С.</copyright-holder><copyright-holder xml:lang="en">Petrov V.I., Anikeev I.S., Zayachnikova T.E., Strygin A.V., Kurkin D.V., Kazmina Y.S.</copyright-holder><license xml:lang="ru" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>Данная работа распространяется под лицензией Creative Commons Attribution 4.0.</license-p></license><license xml:lang="en" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>This work is licensed under a Creative Commons Attribution 4.0 License.</license-p></license></permissions><self-uri xlink:href="https://www.pharmpharm.ru/jour/article/view/1381">https://www.pharmpharm.ru/jour/article/view/1381</self-uri><abstract><p>Терапевтический лекарственный мониторинг (ТЛМ) используется для повышения индивидуализации фармакотерапии, особенного у групп пациентов с высокой межиндивидуальной вариабельностью фармакокинетических (ФК) параметров. Одной из таких групп пациентов являются новорожденные дети, для которых лекарственная терапия, особенного препаратами с узким терапевтическим диапазоном, вызывает ряд трудностей или не может быть применена в принципе.</p><sec><title>Цель</title><p>Цель. Разработка и валидация методов количественного ВЭЖХ-МС/МС определения ванкомицина в образцах «высушенной капли крови» с использованием новых протоколов и сравнение полученных данных с результатами в образцах плазмы с использованием стандартных методов пробоподготовки.</p></sec><sec><title>Материалы и методы</title><p>Материалы и методы. Для приготовления маточных и стандартных растворов ванкомицина и норванкомицина как внутреннего стандарта использовали сухие навески соответствующих сертифицированных стандартов ванкомицина (Servier, Франция) и норванкомицина (Augsburg, Германия, степ. чистоты &gt;95,0%). Хроматографическое разделение компонентов проводили на колонке Poroshell 120 C18 (4,6×50 мм, 2,7 мкм). При разработке условий масс-спектрометрической детекции искомых веществ методом мониторинга множественных реакций (MRM) были определены ионы-предшественники и соответствующие им ионы-продукты.</p></sec><sec><title>Результаты</title><p>Результаты. Разработана и валидирована методика количественного ВЭЖХ-МС/МС определения ванкомицина в образцах «высушенной капли». Провели сравнение между значениями концентраций ванкомицина в образцах «высушенной капли крови» и образцах плазмы. При этом более 95% рассчитанных средних концентраций находились в пределах d-2s и d+2s, которые соответствовали значениям –10,2 и 12,2, что подтверждало пригодность разработанного метода для анализа образцов пациентов.</p></sec><sec><title>Заключение</title><p>Заключение. Полученные результаты позволяют рекомендовать метод «высушенной капли крови» для проведения терапевтического мониторинга ванкомицина, дополнительных исследований ФК у данной группы пациентов с последующим применением данного лекарственного препарата у новорожденных и пациентов детского возраста.</p></sec></abstract><trans-abstract xml:lang="en"><p>Therapeutic drug monitoring (TDM) is used to increase the individualization of pharmacotherapy, especially in patient groups with a high interindividual variability in pharmacokinetic (PK) parameters. One of these groups of patients is newborn children, for whom drug therapy, especially drugs with a narrow therapeutic range, causes a few difficulties or cannot be used in principle.</p><p>The aim of the work was to develop and validate quantitative HPLC-MS/MS methods for the determination of vancomycin in “dried blood spot” samples using new protocols and comparison of the results obtained with the results in plasma samples using standard sample preparation methods.</p><sec><title>Materials and methods</title><p>Materials and methods. To prepare stock and standard solutions of vancomycin and norvancomycin as an internal standard, dry portions of the corresponding certified standards of vancomycin (Servier, France) and norvancomycin (Augsburg, Germany, purity grade &gt;95.0%) were used. A chromatographic separation of the components was carried out on a Poroshell 120 C18 column (4.6×50 mm, 2.7 µm). When developing conditions for a mass spectrometric detection of the desired substances using the multiple reaction monitoring (MRM) method, precursor ions and their corresponding product ions were determined.</p></sec><sec><title>Results</title><p>Results. A quantitative HPLC-MS/MS method for the determination of vancomycin in «dried blood spot» samples was developed and validated. A comparison was made between vancomycin concentrations in «dried blood spot» samples and plasma samples. Moreover, more than 95% of the calculated average concentrations are within the limits of d-2s and d+2s, which correspond to the values of –10.2 and 12.2. That confirms the suitability of the developed method for the analysis of patient samples.</p></sec><sec><title>Conclusion</title><p>Conclusion. The results obtained make it possible for us to recommend the “dried blood spot” method for therapeutic monitoring of vancomycin, additional studies of PK in this group of patients with subsequent use of this drug in newborns and pediatric patients.</p></sec></trans-abstract><kwd-group xml:lang="ru"><kwd>терапевтический лекарственный мониторинг</kwd><kwd>ванкомицин</kwd><kwd>ВЭЖХ/МС</kwd><kwd>валидация</kwd><kwd>биоаналитика</kwd><kwd>метод «высушенной капли крови»</kwd></kwd-group><kwd-group xml:lang="en"><kwd>therapeutic drug monitoring</kwd><kwd>vancomycin</kwd><kwd>HPLC/MS</kwd><kwd>validation</kwd><kwd>bioanalytics</kwd><kwd>dried blood spot method</kwd></kwd-group><funding-group><funding-statement xml:lang="ru">Работа выполнена в рамках Гранта РНФ по теме: «Разработка популяционной фармакостатистической модели для оценки прогностической значимости факторов вариабельности параметров фармакокинетики антибактериальных препаратов у новорождённых», в рамках соглашения от 10 июня 2022 года № 11 (на проведение фундаментальных научных исследований и поисковых научных исследований) между Комитетом экономической политики и развития Волгоградской области, Российским научным фондом и федеральным государственным бюджетным образовательным учреждением высшего образования «Волгоградский государственный медицинский университет» Министерства здравоохранения Российской Федерации, а также руководителем научного коллектива.</funding-statement><funding-statement xml:lang="en">The work has been carried out within the framework of the Russian Science Foundation Grant – “Development of a population pharmacostatistical model to assess the prognostic significance of the variability factors of the pharmacokinetics parameters of the of antibacterial drugs in newborns”, under the Agreement No. 11 dated June 10, 2022 (for conducting fundamental scientific research and exploratory scientific research) between the Committee for Economic Policy and Development of the Volgograd Region, Russian Scientific Foundation and Volgograd State Medical University and the head of the research team.</funding-statement></funding-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">Толкачев Б.Е., Петров В.И., Заячникова Т.Е., Стрыгин А.В., Аникеев И.С., Доценко А.М. 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