<?xml version="1.0" encoding="UTF-8"?>
<!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.3 20210610//EN" "JATS-journalpublishing1-3.dtd">
<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">vedomostiregmed</journal-id><journal-title-group><journal-title xml:lang="ru">Регуляторные исследования и экспертиза лекарственных средств</journal-title><trans-title-group xml:lang="en"><trans-title>Regulatory Research and Medicine Evaluation</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">3034-3062</issn><issn pub-type="epub">3034-3453</issn><publisher><publisher-name>Federal State Budgetary Institution ‘Scientific Centre for Expert Evaluation of Medicinal Products’ of the Ministry of Health of the Russian Federation (FSBI ‘SCEEMP’)</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.30895/1991-2919-2023-13-4-567-577</article-id><article-id custom-type="elpub" pub-id-type="custom">vedomostiregmed-567</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>ИНСТРУМЕНТАЛЬНЫЕ МЕТОДЫ</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>INSTRUMENTAL METHODS</subject></subj-group></article-categories><title-group><article-title>Современные методы идентификации и количественного определения сердечных гликозидов</article-title><trans-title-group xml:lang="en"><trans-title>Modern methods for identification and quantification of cardiac glycosides</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-2191-1033</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Евдокимова</surname><given-names>О. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Evdokimova</surname><given-names>O. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Евдокимова Ольга Владимировна, доктор фарм. наук, доцент</p><p>Петровский б-р, д. 8, стр. 2, Москва, 127051, Российская Федерация</p></bio><bio xml:lang="en"><p>Olga V. Evdokimova, Dr. Sci. (Pharm.), Associate Professor</p><p>8/2 Petrovsky Blvd, Moscow 127051, Russian Federation</p></bio><email xlink:type="simple">evdokimovaov@expmed.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/0000-0001-6975-516X</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Бекетова</surname><given-names>А. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Beketova</surname><given-names>A. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Бекетова Анастасия Викторовна, канд. фарм. наук</p><p>Петровский б-р, д. 8, стр. 2, Москва, 127051, Российская Федерация</p></bio><bio xml:lang="en"><p>Anastasia V. Beketova, Сand. Sci. (Pharm.)</p><p>8/2 Petrovsky Blvd, Moscow 127051, Russian Federation</p></bio><email xlink:type="simple">beketova@expmed.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/0000-0003-1289-4307</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Наумова</surname><given-names>О. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Naumova</surname><given-names>O. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Наумова Ольга Анатольевна, канд. фарм. наук</p><p>Петровский б-р, д. 8, стр. 2, Москва, 127051, Российская Федерация</p></bio><bio xml:lang="en"><p>Olga A. Naumova, Сand. Sci. (Pharm.)</p><p>8/2 Petrovsky Blvd, Moscow 127051, Russian Federation</p></bio><email xlink:type="simple">naumovaoa@expmed.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/0009-0001-9627-1395</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Клинкова</surname><given-names>И. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Klinkova</surname><given-names>I. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Клинкова Ирина Васильевна</p><p>Петровский б-р, д. 8, стр. 2, Москва, 127051, Российская Федерация</p></bio><bio xml:lang="en"><p>Irina V. Klinkova</p><p>8/2 Petrovsky Blvd, Moscow 127051, Russian Federation</p></bio><email xlink:type="simple">klinkovaiv@expmed.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/0000-0003-3720-9687</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Шемерянкина</surname><given-names>Т. Б.</given-names></name><name name-style="western" xml:lang="en"><surname>Shemeryankina</surname><given-names>T. B.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Шемерянкина Татьяна Борисовна, канд. фарм. наук</p><p>Петровский б-р, д. 8, стр. 2, Москва, 127051, Российская Федерация</p></bio><bio xml:lang="en"><p>Tatiana B. Shemeryankina, Cand. Sci.  (Pharm.)</p><p>8/2 Petrovsky Blvd, Moscow 127051, Russian Federation</p></bio><email xlink:type="simple">shemeryankina@expmed.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/0000-0003-4551-8252</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Ладыгина</surname><given-names>Л. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Ladygina</surname><given-names>L. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Ладыгина Лиана Александровна</p><p>Петровский б-р, д. 8, стр. 2, Москва, 127051, Российская Федерация</p></bio><bio xml:lang="en"><p>Liana A. Ladygina</p><p>8/2 Petrovsky Blvd, Moscow 127051, Russian Federation</p></bio><email xlink:type="simple">ladygina@expmed.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/0009-0006-2928-9858</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Бущик</surname><given-names>К. С.</given-names></name><name name-style="western" xml:lang="en"><surname>Bushchik</surname><given-names>K. S.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Бущик Кристина Сергеевна </p><p>Петровский б-р, д. 8, стр. 2, Москва, 127051, Российская Федерация</p></bio><bio xml:lang="en"><p>Kristina S. Bushchik </p><p>8/2 Petrovsky Blvd, Moscow 127051, Russian Federation</p></bio><email xlink:type="simple">bushchikks@expmed.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 учреждение  «Научный центр экспертизы средств медицинского применения»  Министерства здравоохранения Российской Федерации</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Scientific Centre for Expert Evaluation of Medicinal Products</institution><country>Russian Federation</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2023</year></pub-date><pub-date pub-type="epub"><day>21</day><month>11</month><year>2023</year></pub-date><volume>13</volume><issue>4</issue><fpage>567</fpage><lpage>577</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Евдокимова О.В., Бекетова А.В., Наумова О.А., Клинкова И.В., Шемерянкина Т.Б., Ладыгина Л.А., Бущик К.С., 2023</copyright-statement><copyright-year>2023</copyright-year><copyright-holder xml:lang="ru">Евдокимова О.В., Бекетова А.В., Наумова О.А., Клинкова И.В., Шемерянкина Т.Б., Ладыгина Л.А., Бущик К.С.</copyright-holder><copyright-holder xml:lang="en">Evdokimova O.V., Beketova A.V., Naumova O.A., Klinkova I.V., Shemeryankina T.B., Ladygina L.A., Bushchik K.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.vedomostincesmp.ru/jour/article/view/567">https://www.vedomostincesmp.ru/jour/article/view/567</self-uri><abstract><sec><title>Актуальность</title><p>Актуальность. Сердечные гликозиды более двух столетий находят применение в медицине. Данные современных исследований позволяют рассматривать перспективу применения биологически активных веществ этой группы не только в кардиологии, но и для лечения вирусных, онкологических и других заболеваний. Таким образом, актуальность выбора методов контроля качества сердечных гликозидов возрастает.</p></sec><sec><title>Цель</title><p>Цель. На основе анализа отечественных и зарубежных стандартов качества, а также современных научных данных выявить перспективные методы идентификации и количественного определения сердечных гликозидов в лекарственном растительном сырье (ЛРС) и лекарственных препаратах и оценить возможность использования физико-химических методов взамен биологических.</p></sec><sec><title>Обсуждение</title><p>Обсуждение. Используемые в настоящее время методы стандартизации сердечных гликозидов являются неселективными или предусматривают использование лабораторных животных (биологические тест-системы). При изучении фармакопейных методов идентификации сердечных гликозидов как в ЛРС, так и в составе лекарственных средств было показано, что актуальным остается использование химических методов (качественных реакций) и тонкослойной хроматографии. Установлено, что при количественной оценке ЛРС и экстракционных препаратов из него используются биологические или неселективные (спектрофотометрические) методы, хроматографические методы представлены только в фармакопейных статьях и монографиях на субстанции, содержащие индивидуальные сердечные гликозиды, и лекарственные препараты на их основе. Проведенный анализ стандартов качества и научных публикаций позволил выявить перспективные методы количественного определения сердечных гликозидов как в ЛРС, так и в фармацевтических субстанциях и лекарственных препаратах. Такими методами могут быть хроматографические методы.</p></sec><sec><title>Выводы</title><p>Выводы. Наиболее приемлемым методом для фармакопейного анализа является обращенно-фазовая высокоэффективная жидкостная хроматография (ВЭЖХ) со спектрофотометрическим детектированием. Разработка ВЭЖХ-методики количественного определения сердечных гликозидов позволит перейти от использования биологических или неселективных методов при анализе сердечных гликозидов к современному селективному методу анализа.</p></sec></abstract><trans-abstract xml:lang="en"><sec><title>Scientific relevance</title><p>Scientific relevance. Cardiac glycosides have been used in medicine for over two centuries. Current studies suggest that biologically active substances from this group can be used to treat not only heart conditions but also viral infections, cancers, and other diseases. Therefore, quality control methods for cardiac glycosides are becoming increasingly relevant.</p></sec><sec><title>Aim</title><p>Aim. Based on a review of Russian and international quality standards, as well as up-to-date scientific data, this study aimed to identify promising methods for the identification and quantification of cardiac glycosides in herbal drugs and herbal medicinal products, as well as to evaluate the possibility of substituting physicochemical methods for biological methods.</p></sec><sec><title>Discussion</title><p>Discussion. The methods that are currently used to standardise cardiac glycosides are either not selective or require laboratory animals (biological test systems). According to a study of pharmacopoeial methods for the identification of cardiac glycosides in herbal drugs and herbal medicinal products, chemical identification tests and thin-layer chromatography continue to be relevant. Quantitative testing of herbal drugs and extracts uses biological and non-selective (spectrophotometry) methods, whereas chromatography is described only in general and individual monographs for herbal drug preparations containing individual cardiac glycosides and medicinal products containing these preparations. Upon analysing quality standards and scientific publications, the authors identified potentially promising methods for the quantification of cardiac glycosides in herbal drugs, herbal drug preparations, and herbal medicinal products, namely chromatographic methods.</p></sec><sec><title>Conclusions</title><p>Conclusions. Reverse-phase high-performance liquid cjromatography (HPLC) with spectrophotometric detection is the most suitable method for pharmacopoeial analysis. The development of an HPLC-based analytical procedure to determine the cardiac glycoside content will provide an opportunity to advance from biological or non-selective methods to more ethical and selective up-to-date techniques.</p></sec></trans-abstract><kwd-group xml:lang="ru"><kwd>лекарственное растительное сырье</kwd><kwd>сердечные гликозиды</kwd><kwd>стандартизация</kwd><kwd>качественные реакции</kwd><kwd>тонкослойная хроматография</kwd><kwd>высокоэффективная жидкостная хроматография</kwd><kwd>фармакопейные требования</kwd></kwd-group><kwd-group xml:lang="en"><kwd>herbal drugs</kwd><kwd>cardiac glycosides</kwd><kwd>standardisation</kwd><kwd>qualitative reactions</kwd><kwd>thin-layer chromatography</kwd><kwd>high-performance liquid chromatography</kwd><kwd>pharmacopoeia</kwd></kwd-group><funding-group><funding-statement xml:lang="ru">Работа выполнена в рамках государственного задания ФГБУ «НЦЭСМП» Минздрава России № 056- 00052-23-00 на проведение прикладных научных исследований (номер государственного учета НИР 121021800098-4)</funding-statement><funding-statement xml:lang="en">The study reported in this publication was carried out as part of publicly funded research project No. 056-00052-23-00 and was supported by the Scientific Centre for Expert Evaluation of Medicinal Products (R&amp;D reporting No. 121021800098-4).</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">Ribeiro WLC, Macedo ITF, Santos JML, Oliveira EF, Camurça-Vasconcelos ALF, Paula HCB, et al. Activity of chitosan-encapsulated Eucalyptus staigeriana essential oil on Haemonchus contortus. Exp Parasitol. 2013;135(1):24–9. https://doi.org/10.1016/j.exppara.2013.05.014</mixed-citation><mixed-citation xml:lang="en">Ribeiro WLC, Macedo ITF, Santos JML, Oliveira EF, Camurça-Vasconcelos ALF, Paula HCB, et al. Activity of chitosan-encapsulated Eucalyptus staigeriana essential oil on Haemonchus contortus. Exp Parasitol. 2013;135(1):24–9. https://doi.org/10.1016/j.exppara.2013.05.014</mixed-citation></citation-alternatives></ref><ref id="cit2"><label>2</label><citation-alternatives><mixed-citation xml:lang="ru">Rietbrock N, Woodcock B. Two hundred years of foxglove therapy Digitalis purpurea 1 785–1985. Trends Pharmacol Sci. 1985;6:267–9. https://doi.org/10.1016/0165-6147(85)90123-3</mixed-citation><mixed-citation xml:lang="en">Rietbrock N, Woodcock B. Two hundred years of foxglove therapy Digitalis purpurea 1 785–1985. Trends Pharmacol Sci. 1985;6:267–9. https://doi.org/10.1016/0165-6147(85)90123-3</mixed-citation></citation-alternatives></ref><ref id="cit3"><label>3</label><citation-alternatives><mixed-citation xml:lang="ru">Wade OL. Digoxin 1785-1985. I. Two hundred years of digitalis. J Clin Hosp Pharm. 1986;11(1):3–9. https://doi.org/10.1111/j.1365-2710.1986.tb00822.x</mixed-citation><mixed-citation xml:lang="en">Wade OL. Digoxin 1785-1985. I. Two hundred years of digitalis. J Clin Hosp Pharm. 1986;11(1):3–9. https://doi.org/10.1111/j.1365-2710.1986.tb00822.x</mixed-citation></citation-alternatives></ref><ref id="cit4"><label>4</label><citation-alternatives><mixed-citation xml:lang="ru">El-Seedi HR, Khalifa SAM, Taher EA, Farag MA, Saeed A, Gamal M, et al. Cardenolides: Insights from chemical structure and pharmacological utility. Pharmacol Res. 2019;141:123–75. https://doi.org/10.1016/j.phrs.2018.12.01</mixed-citation><mixed-citation xml:lang="en">El-Seedi HR, Khalifa SAM, Taher EA, Farag MA, Saeed A, Gamal M, et al. Cardenolides: Insights from chemical structure and pharmacological utility. Pharmacol Res. 2019;141:123–75. https://doi.org/10.1016/j.phrs.2018.12.01</mixed-citation></citation-alternatives></ref><ref id="cit5"><label>5</label><citation-alternatives><mixed-citation xml:lang="ru">Дукельская НК, Гармашова ИВ, Давыдова МВ. Сравнительный анализ препаратов сердечных гликозидов, используемых в современной фармакотерапии. Известия Российской военно-медицинской академии. 2020;39(S3–4):82–5.</mixed-citation><mixed-citation xml:lang="en">Dukelskaya NK, Garmashova IV, Davydova MV. Comparative analysis of the products of cardiac glycosides used in modern pharmacotherapy. Russian Military Medical Academy Report. 2020;39(S3–4):82–5 (In Russ.). EDN: SNCYHH</mixed-citation></citation-alternatives></ref><ref id="cit6"><label>6</label><citation-alternatives><mixed-citation xml:lang="ru">Kanji S, MacLean RD. Cardiac glycoside toxicity: more than 200 years and counting. Crit Care Clin. 2012;28(4):527–35. https://doi.org/10.1016/j.ccc.2012.07.005</mixed-citation><mixed-citation xml:lang="en">Kanji S, MacLean RD. Cardiac glycoside toxicity: more than 200 years and counting. Crit Care Clin. 2012;28(4):527–35. https://doi.org/10.1016/j.ccc.2012.07.005</mixed-citation></citation-alternatives></ref><ref id="cit7"><label>7</label><citation-alternatives><mixed-citation xml:lang="ru">Morsy N. Cardiac glycosides in medicinal plants. In: El-Shemy HA, ed. Aromatic and Medicinal Plants — Back to Nature. London: InTechOpen; 2017. https://doi.org/10.5772/65963</mixed-citation><mixed-citation xml:lang="en">Morsy N. Cardiac glycosides in medicinal plants. In: El- Shemy HA, ed. Aromatic and Medicinal Plants — Back to Nature. London: InTechOpen; 2017. https://doi.org/10.5772/65963</mixed-citation></citation-alternatives></ref><ref id="cit8"><label>8</label><citation-alternatives><mixed-citation xml:lang="ru">Botelho AFM, Pierezan F, Soto-Blanco B, Melo MM. A review of cardiac glycosides: Structure, toxicokinetics, clinical signs, diagnosis and antineoplastic potential. Toxicon. 2019;158:63–8. https://doi.org/10.1016/j.toxicon.2018.11.429</mixed-citation><mixed-citation xml:lang="en">Botelho AFM, Pierezan F, Soto-Blanco B, Melo MM. A review of cardiac glycosides: Structure, toxicokinetics, clinical signs, diagnosis and antineoplastic potential. Toxicon. 2019;158:63–8. https://doi.org/10.1016/j.toxicon.2018.11.429</mixed-citation></citation-alternatives></ref><ref id="cit9"><label>9</label><citation-alternatives><mixed-citation xml:lang="ru">Pongrakhananon V. Anticancer properties of cardiac glycosides. In: Rangel L, ed. Cancer Treatment — Conventional and Innovative Approaches. London: Intechopen; 2013. https://doi.org/10.5772/55381</mixed-citation><mixed-citation xml:lang="en">Pongrakhananon V. Anticancer properties of cardiac glycosides. In: Rangel L, ed. Cancer Treatment — Conventional and Innovative Approaches. London: Intechopen; 2013. https://doi.org/10.5772/55381</mixed-citation></citation-alternatives></ref><ref id="cit10"><label>10</label><citation-alternatives><mixed-citation xml:lang="ru">Гуревич МА, Гаврилин АА. Сердечные гликозиды в современной клинической практике. Альманах клинической медицины. 2014;(35):101–5. https://doi.org/10.18786/2072-0505-2014-35-101-105</mixed-citation><mixed-citation xml:lang="en">Gurevich MA, Gavrilin AA. Cardiac glycosides in up-to- date clinical practice. Аlmanac of Clinical Medicine. 2014;(35):101–5 (In Russ.). https://doi.org/10.18786/2072-0505-2014-35-101-105</mixed-citation></citation-alternatives></ref><ref id="cit11"><label>11</label><citation-alternatives><mixed-citation xml:lang="ru">Мареев ВЮ, Агеев ФТ, Арутюнов ГП, Коротеев АВ, Мареев ЮВ, Овчинников АГ и др. Национальные рекомендации ОССН, РКО и РНМОТ по диагностике и лечению ХСН (четвертый пересмотр). Сердечная недостаточность. 2013;14(7):372–9.</mixed-citation><mixed-citation xml:lang="en">Mareev VYu, Ageev FT, Arutyunov GP, Koroteev AV, Mareev YuV, Ovchinnikov AG, et al. SEHF, RSC AND RSMSIM National guidelines on CHF diagnostics and treatment (fourth revision). Heart Failure. 2013;14(7):372–9 (In Russ.). EDN: VHDBDT</mixed-citation></citation-alternatives></ref><ref id="cit12"><label>12</label><citation-alternatives><mixed-citation xml:lang="ru">Philippe G, Angenot L. Recent developments in the field of arrow and dart poisons. J. Ethnopharmacol. 2005;100(1–2):85–91. https://doi.org/10.1016/j.jep.2005.05.022</mixed-citation><mixed-citation xml:lang="en">Philippe G, Angenot L. Recent developments in the field of arrow and dart poisons. J. Ethnopharmacol. 2005;100(1–2):85–91. https://doi.org/10.1016/j.jep.2005.05.022</mixed-citation></citation-alternatives></ref><ref id="cit13"><label>13</label><citation-alternatives><mixed-citation xml:lang="ru">Bertol W, Rigotto C, Maia de Pádua R, Kreis W, Monte Barardi CR, Braga FC, Simões CMO. Antiherpes activity of glucoevatromonoside, a cardenolide isolated from a Brazilian cultivar of Digitalis lanata. Antiviral Res. 2011;92(1):73–80. https://doi.org/10.1016/j.antiviral.2011.06.015</mixed-citation><mixed-citation xml:lang="en">Bertol W, Rigotto C, Maia de Pádua R, Kreis W, Monte Barardi CR, Braga FC, Simões CMO. Antiherpes activity of glucoevatromonoside, a cardenolide isolated from a Brazilian cultivar of Digitalis lanata. Antiviral Res. 2011;92(1):73–80. https://doi.org/10.1016/j.antiviral.2011.06.015</mixed-citation></citation-alternatives></ref><ref id="cit14"><label>14</label><citation-alternatives><mixed-citation xml:lang="ru">Zhyvoloup A, Melamed A, Anderson I, Planas D, Lee C-H, Kriston-Vizi J, et al. Digoxin reveals a functional connection between HIV-1 integration preference and T-cell activation. PLoS Pathog. 2017;13(7):e1006460. https://doi.org/10.1371/journal.ppat.1006460</mixed-citation><mixed-citation xml:lang="en">Zhyvoloup A, Melamed A, Anderson I, Planas D, Lee C-H, Kriston-Vizi J, et al. Digoxin reveals a functional connection between HIV-1 integration preference and T-cell activation. PLoS Pathog. 2017;13(7):e1006460. https://doi.org/10.1371/journal.ppat.1006460</mixed-citation></citation-alternatives></ref><ref id="cit15"><label>15</label><citation-alternatives><mixed-citation xml:lang="ru">Wong RW, Balachandran A, Ostrowski MA, Cochrane A. Digoxin suppresses HIV-1 replication by altering viral RNA processing. PLoS Pathog. 2013;9(3):e1003241. https://doi.org/10.1371/journal.ppat.1003241</mixed-citation><mixed-citation xml:lang="en">Wong RW, Balachandran A, Ostrowski MA, Cochrane A. Digoxin suppresses HIV-1 replication by altering viral RNA processing. PLoS Pathog. 2013;9(3):e1003241. https://doi.org/10.1371/journal.ppat.1003241</mixed-citation></citation-alternatives></ref><ref id="cit16"><label>16</label><citation-alternatives><mixed-citation xml:lang="ru">Grosso F, Stoilov P, Lingwood C, Brown M, Cochrane A. Suppression of adenovirus replication by cardiotonic steroids. J Virol. 2017;91(3):e01623-16. https://doi.org/10.1128/jvi.01623-16</mixed-citation><mixed-citation xml:lang="en">Grosso F, Stoilov P, Lingwood C, Brown M, Cochrane A. Suppression of adenovirus replication by cardiotonic steroids. J Virol. 2017;91(3):e01623-16. https://doi.org/10.1128/jvi.01623-16</mixed-citation></citation-alternatives></ref><ref id="cit17"><label>17</label><citation-alternatives><mixed-citation xml:lang="ru">Wang JKT, Portbury S, Thomas MB, Barney S, Ricca DJ, Morris DL, et al. Cardiac glycosides provide neuroprotection against ischemic stroke: Discovery by a brain slice-based compound screening platform. Proc Natl Acad Sci USA. 2006;103(27):10461–6. https://doi.org/10.1073/pnas.0600930103</mixed-citation><mixed-citation xml:lang="en">Wang JKT, Portbury S, Thomas MB, Barney S, Ricca DJ, Morris DL, et al. Cardiac glycosides provide neuroprotection against ischemic stroke: Discovery by a brain slice-based compound screening platform. Proc Natl Acad Sci USA. 2006;103(27):10461–6. https://doi.org/10.1073/pnas.0600930103</mixed-citation></citation-alternatives></ref><ref id="cit18"><label>18</label><citation-alternatives><mixed-citation xml:lang="ru">Пеннияйнен ВА, Плахова ВБ, Подзорова СА, Терехин СГ, Крылов БВ. Возможная физиологическая функция эндогенного уабаина. Интегративная физиология. 2021;2(1):96–101.</mixed-citation><mixed-citation xml:lang="en">Penniyainen VA, Plakhova VB, Podzorova SA, Terekhin SG, Krylov BV. Possible physiological function of endogenous ouabain. Integrative Physiology. 2021;2(1):96–101 (In Russ.). https://doi.org/10.33910/2687-1270-2021-2-1-96-101</mixed-citation></citation-alternatives></ref><ref id="cit19"><label>19</label><citation-alternatives><mixed-citation xml:lang="ru">Kulikov A, Eva A, Kirch U, Boldyrev A, Scheiner-Bobis G. Ouabain activates signaling pathways associated with cell death in human neuroblastoma. Biochim Biophys Acta. 2007;1768(7):1691–702. https://doi.org/10.1016/j.bbamem.2007.04.012</mixed-citation><mixed-citation xml:lang="en">Kulikov A, Eva A, Kirch U, Boldyrev A, Scheiner-Bobis G. Ouabain activates signaling pathways associated with cell death in human neuroblastoma. Biochim Biophys Acta. 2007;1768(7):1691–702. https://doi.org/10.1016/j.bbamem.2007.04.012</mixed-citation></citation-alternatives></ref><ref id="cit20"><label>20</label><citation-alternatives><mixed-citation xml:lang="ru">Lin SY, Chang HH, Lai YH, Lin CH, Chen MH, Chang GC, et al. Digoxin suppresses tumor malignancy through inhibiting multiple Src-related signaling pathways in non-small cell lung cancer. PLoS One. 2015;10(5):e0123305. https://doi.org/10.1371/journal.pone.0123305</mixed-citation><mixed-citation xml:lang="en">Lin SY, Chang HH, Lai YH, Lin CH, Chen MH, Chang GC, et al. Digoxin suppresses tumor malignancy through inhibiting multiple Src-related signaling pathways in non-small cell lung cancer. PLoS One. 2015;10(5):e0123305. https://doi.org/10.1371/journal.pone.0123305</mixed-citation></citation-alternatives></ref><ref id="cit21"><label>21</label><citation-alternatives><mixed-citation xml:lang="ru">Mijatovic T, Mathieu V, Gaussin JF, De Neve N, Ribaucour F, Van Quaquebeke, et al. Cardenolide-induced lysosomal membrane permeabilization demonstrates therapeutic benefits in experimental human non-small cell lung cancers. Neoplasia. 2006;8(5):402–12. https://doi.org/10.1593/neo.05850</mixed-citation><mixed-citation xml:lang="en">Mijatovic T, Mathieu V, Gaussin JF, De Neve N, Ribaucour F, Van Quaquebeke, et al. Cardenolide-induced lysosomal membrane permeabilization demonstrates therapeutic benefits in experimental human non-small cell lung cancers. Neoplasia. 2006;8(5):402–12. https://doi.org/10.1593/neo.05850</mixed-citation></citation-alternatives></ref><ref id="cit22"><label>22</label><citation-alternatives><mixed-citation xml:lang="ru">Mijatovic T, De Beeck АО, Van Quaquebeke EV, Dewelle J, Darro F, de Launoit Y, Kiss R. The cardenolide UNBS1450 is able to deactivate nuclear factor κB-mediated cytoprotective effects in human non-small cell lung cancer cells. Mol Cancer Ther. 2006;5(2):391–9. https://doi.org/10.1158/1535-7163.mct-05-0367</mixed-citation><mixed-citation xml:lang="en">Mijatovic T, De Beeck АО, Van Quaquebeke EV, Dewelle J, Darro F, de Launoit Y, Kiss R. The cardenolide UNBS1450 is able to deactivate nuclear factor κB-mediated cytoprotective effects in human non-small cell lung cancer cells. Mol Cancer Ther. 2006;5(2):391–9. https://doi.org/10.1158/1535-7163.mct-05-0367</mixed-citation></citation-alternatives></ref><ref id="cit23"><label>23</label><citation-alternatives><mixed-citation xml:lang="ru">Frese S, Frese-Schaper M, Andres AC, Miescher D, Zumkehr B, Schmid RA. Cardiac glycosides initiate Apo2L/TRAIL-induced apoptosis in non-small cell lung cancer cells by up-regulation of death receptors 4 and 5. Cancer Res. 2006;66(11):5867–74. https://doi.org/10.1158/0008-5472.can-05-3544</mixed-citation><mixed-citation xml:lang="en">Frese S, Frese-Schaper M, Andres AC, Miescher D, Zumkehr B, Schmid RA. Cardiac glycosides initiate Apo2L/TRAIL-induced apoptosis in non-small cell lung cancer cells by up-regulation of death receptors 4 and 5. Cancer Res. 2006;66(11):5867–74. https://doi.org/10.1158/0008-5472.can-05-3544</mixed-citation></citation-alternatives></ref><ref id="cit24"><label>24</label><citation-alternatives><mixed-citation xml:lang="ru">Johansson S, Lindholm P, Gullbo J, Larsson R, Bohlin L, Claeson P, et al. Cytotoxicity of digitoxin and related cardiac glycosides in human tumor cells. Anticancer Drugs. 2001;12(5):475–83. https://doi.org/10.1097/00001813-200106000-00009</mixed-citation><mixed-citation xml:lang="en">Johansson S, Lindholm P, Gullbo J, Larsson R, Bohlin L, Claeson P, et al. Cytotoxicity of digitoxin and related cardiac glycosides in human tumor cells. Anticancer Drugs. 2001;12(5):475–83. https://doi.org/10.1097/00001813-200106000-00009</mixed-citation></citation-alternatives></ref><ref id="cit25"><label>25</label><citation-alternatives><mixed-citation xml:lang="ru">McConkey DJ, Lin Y, Nutt LK, Ozel HZ, Newman RA. Cardiac glycosides stimulate Ca2+ increases and apoptosis in androgen-independent, metastatic human prostate adenocarcinoma cells. Cancer Res. 2000;60(14):3807–12. PMID: 10919654</mixed-citation><mixed-citation xml:lang="en">McConkey DJ, Lin Y, Nutt LK, Ozel HZ, Newman RA. Cardiac glycosides stimulate Ca2+ increases and apoptosis in androgen-independent, metastatic human prostate adenocarcinoma cells. Cancer Res. 2000;60(14):3807–12. PMID: 10919654</mixed-citation></citation-alternatives></ref><ref id="cit26"><label>26</label><citation-alternatives><mixed-citation xml:lang="ru">Huang YT, Chueh SC, Teng CM, Guh JH. Investigation of ouabain-induced anticancer effect in human androgen-independent prostate cancer PC-3 cells. Biochem Pharmacol. 2004;67(4):727–33. https://doi.org/10.1016/j.bcp.2003.10.013</mixed-citation><mixed-citation xml:lang="en">Huang YT, Chueh SC, Teng CM, Guh JH. Investigation of ouabain-induced anticancer effect in human androgen- independent prostate cancer PC-3 cells. Biochem Pharmacol. 2004;67(4):727–33. https://doi.org/10.1016/j.bcp.2003.10.013</mixed-citation></citation-alternatives></ref><ref id="cit27"><label>27</label><citation-alternatives><mixed-citation xml:lang="ru">Yeh JY, Huang WJ, Kan SF, Wang PS. Effects of bufalin and cinobufagin on the proliferation of androgen dependent and independent prostate cancer cells. Prostat. 2003;54(2):112–24. https://doi.org/10.1002/pros.10172</mixed-citation><mixed-citation xml:lang="en">Yeh JY, Huang WJ, Kan SF, Wang PS. Effects of bufalin and cinobufagin on the proliferation of androgen dependent and independent prostate cancer cells. Prostat. 2003;54(2):112–24. https://doi.org/10.1002/pros.10172</mixed-citation></citation-alternatives></ref><ref id="cit28"><label>28</label><citation-alternatives><mixed-citation xml:lang="ru">Chen JQ, Contreras RG, Wang R, Fernandez SV, Shoshani L, Russo IH, et al. Sodium/potasium ATPase (Na+, K+-ATPase) and ouabain/related cardiac glycosides: A new paradigm for development of anti-breast cancer drugs. Breast Cancer Res Treat. 2006;96(1):1–15. https://doi.org/10.1007/s10549-005-9053-3</mixed-citation><mixed-citation xml:lang="en">Chen JQ, Contreras RG, Wang R, Fernandez SV, Shoshani L, Russo IH, et al. Sodium/potasium ATPase (Na+, K+-ATPase) and ouabain/related cardiac glycosides: A new paradigm for development of anti-breast cancer drugs. Breast Cancer Res Treat. 2006;96(1):1–15. https://doi.org/10.1007/s10549-005-9053-3</mixed-citation></citation-alternatives></ref><ref id="cit29"><label>29</label><citation-alternatives><mixed-citation xml:lang="ru">Bielawski К, Winnicka К, Bielawska А. Inhibition of DNA topoisomerases I and II, and growth inhibition of breast cancer MCF-7 cells by ouabain, digoxin and proscillaridin. Biol Pharm Bull. 2006;29(7):1493–7. https://doi.org/10.1248/bpb.29.1493</mixed-citation><mixed-citation xml:lang="en">Bielawski К, Winnicka К, Bielawska А. Inhibition of DNA topoisomerases I and II, and growth inhibition of breast cancer MCF-7 cells by ouabain, digoxin and proscillaridin. Biol Pharm Bull. 2006;29(7):1493–7. https://doi.org/10.1248/bpb.29.1493</mixed-citation></citation-alternatives></ref><ref id="cit30"><label>30</label><citation-alternatives><mixed-citation xml:lang="ru">Lopez-Lazaro M, Pastor N, Azrak SS, Ayuso MJ, Austin CA, Cortes F. Digitoxin inhibits the growth of cancer cell lines at concentrations commonly found in cardiac patients. J Nat Prod. 2005;68(11):1642–5. https://doi.org/10.1021/np050226l</mixed-citation><mixed-citation xml:lang="en">Lopez-Lazaro M, Pastor N, Azrak SS, Ayuso MJ, Austin CA, Cortes F. Digitoxin inhibits the growth of cancer cell lines at concentrations commonly found in cardiac patients. J Nat Prod. 2005;68(11):1642–5. https://doi.org/10.1021/np050226l</mixed-citation></citation-alternatives></ref><ref id="cit31"><label>31</label><citation-alternatives><mixed-citation xml:lang="ru">Newman RA, Yang Р, Hittelman WN, Lu T, Ho DH, Ni D, et al. Oleandrin-mediated oxidative stress in human melanoma cells. J Exp Ther Oncol. 2006;5(3):167–81. PMID: 16528968</mixed-citation><mixed-citation xml:lang="en">Newman RA, Yang Р, Hittelman WN, Lu T, Ho DH, Ni D, et al. Oleandrin-mediated oxidative stress in human melanoma cells. J Exp Ther Oncol. 2006;5(3):167–81. PMID: 16528968</mixed-citation></citation-alternatives></ref><ref id="cit32"><label>32</label><citation-alternatives><mixed-citation xml:lang="ru">Masuda Y, Kawazoe N, Nakajo S, Yoshida T, Kuroiwa Y, Nakaya K. Bufalin induces apoptosis and influences the expression of apoptosis-related genes in human leukemia cells. Leuk Res. 1995;19(8):549–56. https://doi.org/10.1016/0145-2126(95)00031-i</mixed-citation><mixed-citation xml:lang="en">Masuda Y, Kawazoe N, Nakajo S, Yoshida T, Kuroiwa Y, Nakaya K. Bufalin induces apoptosis and influences the expression of apoptosis-related genes in human leukemia cells. Leuk Res. 1995;19(8):549–56. https://doi.org/10.1016/0145-2126(95)00031-i</mixed-citation></citation-alternatives></ref><ref id="cit33"><label>33</label><citation-alternatives><mixed-citation xml:lang="ru">Jing Y, Ohizumi H, Kawazoe N, Hashimoto S, Masuda Y, Nakajo S, et al. Selective inhibitory effect of bufalin on growth of human tumor cells in vitro: association with the induction of apoptosis in leukemia HL-60 cells. Jpn J Cancer Res. 1994;85(6):645–51. https://doi.org/10.1111/j.1349-7006.1994.tb02408.x</mixed-citation><mixed-citation xml:lang="en">Jing Y, Ohizumi H, Kawazoe N, Hashimoto S, Masuda Y, Nakajo S, et al. Selective inhibitory effect of bufalin on growth of human tumor cells in vitro: association with the induction of apoptosis in leukemia HL-60 cells. Jpn J Cancer Res. 1994;85(6):645–51. https://doi.org/10.1111/j.1349-7006.1994.tb02408.x</mixed-citation></citation-alternatives></ref><ref id="cit34"><label>34</label><citation-alternatives><mixed-citation xml:lang="ru">Kawazoe N, Watabe M, Masuda Y, Nakajo S, Nakaya K. Tiam1 is involved in the regulation of bufalin-induced apoptosis in human leukemia cells. Oncogene 1999;18(15):2413–21. https://doi.org/10.1038/sj.onc.1202555</mixed-citation><mixed-citation xml:lang="en">Kawazoe N, Watabe M, Masuda Y, Nakajo S, Nakaya K. Tiam1 is involved in the regulation of bufalin-induced apoptosis in human leukemia cells. Oncogene 1999;18(15):2413–21. https://doi.org/10.1038/sj.onc.1202555</mixed-citation></citation-alternatives></ref><ref id="cit35"><label>35</label><citation-alternatives><mixed-citation xml:lang="ru">Watabe M, Kawazoe N, Masuda Y, Nakajo S, Nakaya K. Bcl-2 protein inhibits bufalin-induced apoptosis through inhibition of mitogen-activated protein kinase activation in human leukemia U937 cells. Cancer Res. 1997;57(15):3097–100. PMID: 9242431</mixed-citation><mixed-citation xml:lang="en">Watabe M, Kawazoe N, Masuda Y, Nakajo S, Nakaya K. Bcl-2 protein inhibits bufalin-induced apoptosis through inhibition of mitogen-activated protein kinase activation in human leukemia U937 cells. Cancer Res. 1997;57(15):3097–100. PMID: 9242431</mixed-citation></citation-alternatives></ref><ref id="cit36"><label>36</label><citation-alternatives><mixed-citation xml:lang="ru">Круглов ДС, Кошкарева КЕ. Количественное определение конваллятоксина в растительном сырье, содержащем кардиостероиды, методом фотометрии. Сибирский медицинский вестник. 2019;(4):34–7.</mixed-citation><mixed-citation xml:lang="en">Kruglov DS, Koshkareva KE. Quantitative estimation of convallatoxin in plant raw material containing cardiosteroids by photometry. Sibirskij Medicinskij Vestnik. 2019;(4):34–7 (In Russ.). EDN: LHXXYU</mixed-citation></citation-alternatives></ref><ref id="cit37"><label>37</label><citation-alternatives><mixed-citation xml:lang="ru">Власенко ЛМ. Определение гликозидов дигиталиса в трупном материале фотометрическим методом на основе реакции взаимодействия с 2,2’,4,4’–тетра-нитродифенилом. Судебно-медицинская экспертиза. 1976;(4):23–7.</mixed-citation><mixed-citation xml:lang="en">Vlasenko LM. Determination of digitalis glycosides in cadaveric material by a photometric method based on the reaction of interaction with 2,2’,4,4’–tetranitrobiphenyl. Forensic Medical Examination. 1976;(4):23–7 (In Russ.).</mixed-citation></citation-alternatives></ref><ref id="cit38"><label>38</label><citation-alternatives><mixed-citation xml:lang="ru">Hassan MHA, Ismail MA, Moharram AM, Shoreit AAM. Phytochemical and antimicrobial of latex serum of Calotropis procera and its silver nanoparticles against some reference pathogenic strains. J Ecol Health Environ. 2017;5(3):65–75. https://doi.org/10.18576/jehe/050301</mixed-citation><mixed-citation xml:lang="en">Hassan MHA, Ismail MA, Moharram AM, Shoreit AAM. Phytochemical and antimicrobial of latex serum of Calotropis procera and its silver nanoparticles against some reference pathogenic strains. J Ecol Health Environ. 2017;5(3):65–75. https://doi.org/10.18576/jehe/050301</mixed-citation></citation-alternatives></ref><ref id="cit39"><label>39</label><citation-alternatives><mixed-citation xml:lang="ru">Galey FD, Holstege DM, Plumlee KH, Tor E, Johnson B, Anderson ML, et al. Diagnosis of oleander poisoning in livestock. J Vet Diagn Invest. 1996;8(3):358–64. https://doi.org/10.1177/104063879600800314</mixed-citation><mixed-citation xml:lang="en">Galey FD, Holstege DM, Plumlee KH, Tor E, Johnson B, Anderson ML, et al. Diagnosis of oleander poisoning in livestock. J Vet Diagn Invest. 1996;8(3):358–64. https://doi.org/10.1177/104063879600800314</mixed-citation></citation-alternatives></ref><ref id="cit40"><label>40</label><citation-alternatives><mixed-citation xml:lang="ru">Hamada K, Iwamoto A, Miyazaki S, Yamanaka N, Guruge KS. Determination of bovine blood oleandrin by high-performance liquid chromatography and postcolumn derivatization. J Chromatogr Sci. 2002;40(9):515–8. https://doi.org/10.1093/chromsci/40.9.555</mixed-citation><mixed-citation xml:lang="en">Hamada K, Iwamoto A, Miyazaki S, Yamanaka N, Guruge KS. Determination of bovine blood oleandrin by high-performance liquid chromatography and postcolumn derivatization. J Chromatogr Sci. 2002;40(9):515–8. https://doi.org/10.1093/chromsci/40.9.555</mixed-citation></citation-alternatives></ref><ref id="cit41"><label>41</label><citation-alternatives><mixed-citation xml:lang="ru">Praveen US, Gowtham MD, Yogaraje-Gowda CV, Nayak VG, Mohan BM. Detection of residues of cardenolides of Nerium oleander by high-performance thinlayer chromatography in autopsy samples. Int J Med Toxicol Forensic Med. 2012;2(4):135–42. https://doi.org/10.22037/ijmtfm.v2i4(Autumn).3758</mixed-citation><mixed-citation xml:lang="en">Praveen US, Gowtham MD, Yogaraje-Gowda CV, Nayak VG, Mohan BM. Detection of residues of cardenolides of Nerium oleander by high-performance thinlayer chromatography in autopsy samples. Int J Med Toxicol Forensic Med. 2012;2(4):135–42. https://doi.org/10.22037/ijmtfm.v2i4(Autumn).3758</mixed-citation></citation-alternatives></ref><ref id="cit42"><label>42</label><citation-alternatives><mixed-citation xml:lang="ru">Tymiak AA, Norman JA, Bolgar M, DiDonato GC, Lee H, Parker WL, et al. Physicochemical characterization of a ouabain isomer isolated from bovine hypothalamus. Proc Natl Acad Sci USA. 1993;90(17):8189–93. https://doi.org/10.1073/pnas.90.17.8189</mixed-citation><mixed-citation xml:lang="en">Tymiak AA, Norman JA, Bolgar M, DiDonato GC, Lee H, Parker WL, et al. Physicochemical characterization of a ouabain isomer isolated from bovine hypothalamus. Proc Natl Acad Sci USA. 1993;90(17):8189–93. https://doi.org/10.1073/pnas.90.17.8189</mixed-citation></citation-alternatives></ref><ref id="cit43"><label>43</label><citation-alternatives><mixed-citation xml:lang="ru">Baecher S, Kroiss M, Fassnacht M, Vogeser M. No endogenous ouabain is detectable in human plasma by ultrasensitive UPLC-MS/MS. Clin Chim Acta. 2014;431:87–92. https://doi.org/10.1016/j.cca.2014.01.038</mixed-citation><mixed-citation xml:lang="en">Baecher S, Kroiss M, Fassnacht M, Vogeser M. No endogenous ouabain is detectable in human plasma by ultrasensitive UPLC-MS/MS. Clin Chim Acta. 2014;431:87–92. https://doi.org/10.1016/j.cca.2014.01.038</mixed-citation></citation-alternatives></ref><ref id="cit44"><label>44</label><citation-alternatives><mixed-citation xml:lang="ru">Bylda C, Thiele R, Kobold U, Volmer DA. Simultaneous quantification of digoxin, digitoxin, and their metabolites in serum using high performance liquid chromatography-tandem mass spectrometry. Drug Test Anal. 2015;7(10):937–46. https://doi.org/10.1002/dta.1781</mixed-citation><mixed-citation xml:lang="en">Bylda C, Thiele R, Kobold U, Volmer DA. Simultaneous quantification of digoxin, digitoxin, and their metabolites in serum using high performance liquid chromatography-tandem mass spectrometry. Drug Test Anal. 2015;7(10):937–46. https://doi.org/10.1002/dta.1781</mixed-citation></citation-alternatives></ref><ref id="cit45"><label>45</label><citation-alternatives><mixed-citation xml:lang="ru">Frommherz L, Köhler H, Brinkmann B, Lehr M, Beike J. LC-MS assay for quantitative determination of cardio glycoside in human blood samples. Int J Legal Med. 2008;122(2):109–14. https://doi.org/10.1007/s00414-007-0175-5</mixed-citation><mixed-citation xml:lang="en">Frommherz L, Köhler H, Brinkmann B, Lehr M, Beike J. LC-MS assay for quantitative determination of cardio glycoside in human blood samples. Int J Legal Med. 2008;122(2):109–14. https://doi.org/10.1007/s00414-007-0175-5</mixed-citation></citation-alternatives></ref><ref id="cit46"><label>46</label><citation-alternatives><mixed-citation xml:lang="ru">Gopal Ravi B, Grace Guardian ME, Dickman R, Wang ZQ. Profiling and structural analysis of cardenolides in two species of Digitalis using liquid chromatography coupled with high-resolution mass spectrometry. J Chromatogr A. 2020:1618:460903. https://doi.org/10.1016/j.chroma.2020.460903</mixed-citation><mixed-citation xml:lang="en">Gopal Ravi B, Grace Guardian ME, Dickman R, Wang ZQ. Profiling and structural analysis of cardenolides in two species of Digitalis using liquid chromatography coupled with high-resolution mass spectrometry. J Chromatogr A. 2020:1618:460903. https://doi.org/10.1016/j.chroma.2020.460903</mixed-citation></citation-alternatives></ref><ref id="cit47"><label>47</label><citation-alternatives><mixed-citation xml:lang="ru">Gosetti F, Nebbia C, Ceci L, Carelli G, Marengo E. UHPLC-MS/MS determination of oleandrin in blood and tissues of dairy cattle poisoned by oleander (Nerium oleander). Anal Methods. 2019;11:5562–7. https://doi.org/10.1039/C9AY01800J</mixed-citation><mixed-citation xml:lang="en">Gosetti F, Nebbia C, Ceci L, Carelli G, Marengo E. UHPLC-MS/MS determination of oleandrin in blood and tissues of dairy cattle poisoned by oleander (Nerium oleander). Anal Methods. 2019;11:5562–7. https://doi.org/10.1039/C9AY01800J</mixed-citation></citation-alternatives></ref><ref id="cit48"><label>48</label><citation-alternatives><mixed-citation xml:lang="ru">Gozalpour E, Greupink R, Bilos A, Verweij V, van den Heuvel J, Masereeuw R, et al. Convallatoxin: A new P-glycoprotein substrate. Eur J Pharmacol. 2014;744:18–27. https://doi.org/10.1016/j.ejphar.2014.09.031</mixed-citation><mixed-citation xml:lang="en">Gozalpour E, Greupink R, Bilos A, Verweij V, van den Heuvel J, Masereeuw R, et al. Convallatoxin: A new P-glycoprotein substrate. Eur J Pharmacol. 2014;744:18–27. https://doi.org/10.1016/j.ejphar.2014.09.031</mixed-citation></citation-alternatives></ref><ref id="cit49"><label>49</label><citation-alternatives><mixed-citation xml:lang="ru">Gozalpour E, Greupink R, Wortelboer HM, Bilos A, Schreurs M, Russel FGM, Koenderink JB. Interaction of digitalis-like compounds with liver uptake transporters NTCP, OATP1B1, a nd O ATP1B3. Mol Pharm. 2014;11(6):1844–55. https://doi.org/10.1021/mp400699p</mixed-citation><mixed-citation xml:lang="en">Gozalpour E, Greupink R, Wortelboer HM, Bilos A, Schreurs M, Russel FGM, Koenderink JB. Interaction of digitalis-like compounds with liver uptake transporters NTCP, OATP1B1, a nd O ATP1B3. Mol Pharm. 2014;11(6):1844–55. https://doi.org/10.1021/mp400699p</mixed-citation></citation-alternatives></ref><ref id="cit50"><label>50</label><citation-alternatives><mixed-citation xml:lang="ru">Grabowski T, Swierczewska A, Borucka B, Sawicka R, Sasinowska-Motyl M, Gumułka SW, et al. А rapid chromatographic/mass spectrometric method for digoxin quantification in human plasma. Pharm Chem J. 2009;43:710–5. https://doi.org/10.1007/s11094-010-0384-y</mixed-citation><mixed-citation xml:lang="en">Grabowski T, Swierczewska A, Borucka B, Sawicka R, Sasinowska-Motyl M, Gumułka SW, et al. А rapid chromatographic/mass spectrometric method for digoxin quantification in human plasma. Pharm Chem J. 2009;43:710–5. https://doi.org/10.1007/s11094-010-0384-y</mixed-citation></citation-alternatives></ref><ref id="cit51"><label>51</label><citation-alternatives><mixed-citation xml:lang="ru">Guan F, Ishii A, Seno H, Watanabe-Suzuki K, Kumazawa T, Suzuki O. Identification and quantification of cardiac glycosides in blood and urine samples by HPLC/ MS/MS. Anal Chem. 1999;71(18):4034–43. https://doi.org/10.1021/ac990268c</mixed-citation><mixed-citation xml:lang="en">Guan F, Ishii A, Seno H, Watanabe-Suzuki K, Kumazawa T, Suzuki O. Identification and quantification of cardiac glycosides in blood and urine samples by HPLC/ MS/MS. Anal Chem. 1999;71(18):4034–43. https://doi.org/10.1021/ac990268c</mixed-citation></citation-alternatives></ref><ref id="cit52"><label>52</label><citation-alternatives><mixed-citation xml:lang="ru">Josephs RD, Daireaux A, Westwood S, Wielgosz RI. Simultaneous determination of various cardiac glycosides by liquid chromatography-hybrid mass spectrometry for the purity assessment of the therapeutic monitored drug digoxin. J Chromatogr A. 2010;1217(27):4535–43. https://doi.org/10.1016/j.chroma.2010.04.060</mixed-citation><mixed-citation xml:lang="en">Josephs RD, Daireaux A, Westwood S, Wielgosz RI. Simultaneous determination of various cardiac glycosides by liquid chromatography-hybrid mass spectrometry for the purity assessment of the therapeutic monitored drug digoxin. J Chromatogr A. 2010;1217(27):4535–43. https://doi.org/10.1016/j.chroma.2010.04.060</mixed-citation></citation-alternatives></ref><ref id="cit53"><label>53</label><citation-alternatives><mixed-citation xml:lang="ru">Kohls S, Scholz-Bottcher B, Rullkotter J, Teske J. Method validation of a survey of thevetia cardiac glycosides in serum samples. Forensic Sci Int. 2012;215(1–3):146–51. https://doi.org/10.1016/j.forsciint.2011.02.013</mixed-citation><mixed-citation xml:lang="en">Kohls S, Scholz-Bottcher B, Rullkotter J, Teske J. Method validation of a survey of thevetia cardiac glycosides in serum samples. Forensic Sci Int. 2012;215(1–3):146–51. https://doi.org/10.1016/j.forsciint.2011.02.013</mixed-citation></citation-alternatives></ref><ref id="cit54"><label>54</label><citation-alternatives><mixed-citation xml:lang="ru">Liang X, Christensen JH, Nielsen JN. Enhancing the power of liquid chromatography — Mass spectrometry for chemical fingerprinting of phytotoxins in the environment. J Chromatogr A. 2021;1642:462027. https://doi.org/10.1016/j.chroma.2021.462027</mixed-citation><mixed-citation xml:lang="en">Liang X, Christensen JH, Nielsen JN. Enhancing the power of liquid chromatography — Mass spectrometry for chemical fingerprinting of phytotoxins in the environment. J Chromatogr A. 2021;1642:462027. https://doi.org/10.1016/j.chroma.2021.462027</mixed-citation></citation-alternatives></ref><ref id="cit55"><label>55</label><citation-alternatives><mixed-citation xml:lang="ru">Malysheva SV, Mulder PPJ, Masquelier J. Development and validation of a UHPLC-ESI-MS/MS method for quantification of oleandrin and other cardiac glycosides and evaluation of their levels in herbs and spices from the Belgian market. Toxins (Basel). 2020;12(4):243. https://doi.org/10.3390/toxins12040243</mixed-citation><mixed-citation xml:lang="en">Malysheva SV, Mulder PPJ, Masquelier J. Development and validation of a UHPLC-ESI-MS/MS method for quantification of oleandrin and other cardiac glycosides and evaluation of their levels in herbs and spices from the Belgian market. Toxins (Basel). 2020;12(4):243. https://doi.org/10.3390/toxins12040243</mixed-citation></citation-alternatives></ref><ref id="cit56"><label>56</label><citation-alternatives><mixed-citation xml:lang="ru">Mitamura K, Horikawa A, Yamane Y, Ikeda Y, Fujii Y, Shimada K. Determination of digoxin in human serum using stable isotope dilution liquid chromatography/ electrospray ionization-tandem mass spectrometry. Biol Pharm Bull. 2007;30(9):1653–6. https://doi.org/10.1248/bpb.30.1653</mixed-citation><mixed-citation xml:lang="en">Mitamura K, Horikawa A, Yamane Y, Ikeda Y, Fujii Y, Shimada K. Determination of digoxin in human serum using stable isotope dilution liquid chromatography/ electrospray ionization-tandem mass spectrometry. Biol Pharm Bull. 2007;30(9):1653–6. https://doi.org/10.1248/bpb.30.1653</mixed-citation></citation-alternatives></ref><ref id="cit57"><label>57</label><citation-alternatives><mixed-citation xml:lang="ru">Rubini S, Rossi SS, Mestria S, Odoardi S, Chendi S, Poli A, et al. A probable fatal case of oleander (Nerium oleander) poisoning on a cattle farm: a new method of detection and quantification of the oleandrin toxin in rumen. Toxins (Basel). 2019;11(8):442. https://doi.org/10.3390/toxins11080442</mixed-citation><mixed-citation xml:lang="en">Rubini S, Rossi SS, Mestria S, Odoardi S, Chendi S, Poli A, et al. A probable fatal case of oleander (Nerium oleander) poisoning on a cattle farm: a new method of detection and quantification of the oleandrin toxin in rumen. Toxins (Basel). 2019;11(8):442. https://doi.org/10.3390/toxins11080442</mixed-citation></citation-alternatives></ref><ref id="cit58"><label>58</label><citation-alternatives><mixed-citation xml:lang="ru">Yadav PB, Lekhak UM, Ghane SG, Lekhak MM. Phytochemicals, antioxidants, estimation of cardiac glycoside (Scillaren A) and detection of major metabolites using LC-MS from Drimia species. S Afr J Bot. 2021;140:259–68. https://doi.org/10.1016/j.sajb.2020.05.002</mixed-citation><mixed-citation xml:lang="en">Yadav PB, Lekhak UM, Ghane SG, Lekhak MM. Phytochemicals, antioxidants, estimation of cardiac glycoside (Scillaren A) and detection of major metabolites using LC-MS from Drimia species. S Afr J Bot. 2021;140:259–68. https://doi.org/10.1016/j.sajb.2020.05.002</mixed-citation></citation-alternatives></ref><ref id="cit59"><label>59</label><citation-alternatives><mixed-citation xml:lang="ru">Zhai JX, Yan H, Shen M, Shen BH, Liu W. Determination of oleandrin in blood and liver samples by LC-MS/ MS. Fa Yi Xue Za Zhi. 2018;34(6):585–9. https://doi.org/10.12116/j.issn.1004-5619.2018.06.002</mixed-citation><mixed-citation xml:lang="en">Zhai JX, Yan H, Shen M, Shen BH, Liu W. Determination of oleandrin in blood and liver samples by LC-MS/ MS. Fa Yi Xue Za Zhi. 2018;34(6):585–9. https://doi.org/10.12116/j.issn.1004-5619.2018.06.002</mixed-citation></citation-alternatives></ref><ref id="cit60"><label>60</label><citation-alternatives><mixed-citation xml:lang="ru">Amitava D, Pradip D. Rapid detection of oleander poisoning using digoxin immunoassays comparison of five assays. Ther Drug Monit. 2004;26(6):658–63. https://doi.org/10.1097/00007691-200412000-00012</mixed-citation><mixed-citation xml:lang="en">Amitava D, Pradip D. Rapid detection of oleander poisoning using digoxin immunoassays comparison of five assays. Ther Drug Monit. 2004;26(6):658–63. https://doi.org/10.1097/00007691-200412000-00012</mixed-citation></citation-alternatives></ref><ref id="cit61"><label>61</label><citation-alternatives><mixed-citation xml:lang="ru">Solnica B. Comparison of serum digoxin concentration monitoring by fluorescence polarization immunoassay on the TDxFLx and dry chemistry enzyme immunoassay on the Vitros 950. Clin Chem Lab Med. 2004;42(8):958–64. https://doi.org/10.1515/CCLM.2004.156</mixed-citation><mixed-citation xml:lang="en">Solnica B. Comparison of serum digoxin concentration monitoring by fluorescence polarization immunoassay on the TDxFLx and dry chemistry enzyme immunoassay on the Vitros 950. Clin Chem Lab Med. 2004;42(8):958–64. https://doi.org/10.1515/CCLM.2004.156</mixed-citation></citation-alternatives></ref><ref id="cit62"><label>62</label><citation-alternatives><mixed-citation xml:lang="ru">Züst T, Petschenka G, Hastings AP, Agrawal AA. Toxicity of milkweed leaves and latex: chromatographic quantification versus biological activity of cardenolides in 16 Asclepias species. J Chem Ecol. 2019;45(1):50–60. https://doi.org/10.1007/s10886-018-1040-3</mixed-citation><mixed-citation xml:lang="en">Züst T, Petschenka G, Hastings AP, Agrawal AA. Toxicity of milkweed leaves and latex: chromatographic quantification versus biological activity of cardenolides in 16 Asclepias species. J Chem Ecol. 2019;45(1):50–60. https://doi.org/10.1007/s10886-018-1040-3</mixed-citation></citation-alternatives></ref><ref id="cit63"><label>63</label><citation-alternatives><mixed-citation xml:lang="ru">Dasgupta А, Bourgeois L. Convallatoxin, the active cardiac glycoside of lily of the valley, minimally affects the ADVIA Centaur digoxin assay. J Clin Lab Anal. 2018;32(8):e22583. https://doi.org/10.1002/jcla.22583</mixed-citation><mixed-citation xml:lang="en">Dasgupta А, Bourgeois L. Convallatoxin, the active cardiac glycoside of lily of the valley, minimally affects the ADVIA Centaur digoxin assay. J Clin Lab Anal. 2018;32(8):e22583. https://doi.org/10.1002/jcla.22583</mixed-citation></citation-alternatives></ref><ref id="cit64"><label>64</label><citation-alternatives><mixed-citation xml:lang="ru">Pellati F, Bruni R, Bellardi MG, Bertaccini A, Benvenuti S. Optimization and validation of a high-performance liquid chromatography method for the analysis of cardiac glycosides in Digitalis lanata. J Chromatogr A. 2009;1216(15):3260–9. https://doi.org/10.1016/j.chroma.2009.02.042</mixed-citation><mixed-citation xml:lang="en">Pellati F, Bruni R, Bellardi MG, Bertaccini A, Benvenuti S. Optimization and validation of a high-performance liquid chromatography method for the analysis of cardiac glycosides in Digitalis lanata. J Chromatogr A. 2009;1216(15):3260–9. https://doi.org/10.1016/j.chroma.2009.02.042</mixed-citation></citation-alternatives></ref><ref id="cit65"><label>65</label><citation-alternatives><mixed-citation xml:lang="ru">Agrawal P, Akhade M, Laddha K, Narkhede S, Mirgal A, Salunke C. Quantification of convallatoxin in Antiaris toxicaria Leusch seeds by RP-HPLC. Anal Chem Lett. 2014;4(3):172–7. https://doi.org/10.1080/22297928.2014.925821</mixed-citation><mixed-citation xml:lang="en">Agrawal P, Akhade M, Laddha K, Narkhede S, Mirgal A, Salunke C. Quantification of convallatoxin in Antiaris toxicaria Leusch seeds by RP-HPLC. Anal Chem Lett. 2014;4(3):172–7. https://doi.org/10.1080/22297928.2014.925821</mixed-citation></citation-alternatives></ref><ref id="cit66"><label>66</label><citation-alternatives><mixed-citation xml:lang="ru">Agrawal AA, Ali А, Johnson MD, Hastings AP, Burge D, Weber MG. Toxicity of the spiny thick-foot Pachypodium. Am J Bot. 2018;105(4):677–86. https://doi.org/10.1002/ajb2.1057</mixed-citation><mixed-citation xml:lang="en">Agrawal AA, Ali А, Johnson MD, Hastings AP, Burge D, Weber MG. Toxicity of the spiny thick-foot Pachypodium. Am J Bot. 2018;105(4):677–86. https://doi.org/10.1002/ajb2.1057</mixed-citation></citation-alternatives></ref><ref id="cit67"><label>67</label><citation-alternatives><mixed-citation xml:lang="ru">Butt AN, Tennant BP, Gillingwater SD, Shepherd PS, Swaminathan R. Binding оf ouabain and human ouabainlike substance to different Na+, K+-ATPase isoforms. Hypertens Res. 2000;23 Suppl:S45–50. https://doi.org/10.1291/hypres.23.supplement_s45</mixed-citation><mixed-citation xml:lang="en">Butt AN, Tennant BP, Gillingwater SD, Shepherd PS, Swaminathan R. Binding оf ouabain and human ouabainlike substance to different Na+, K+-ATPase isoforms. Hypertens Res. 2000;23 Suppl:S45–50. https://doi.org/10.1291/hypres.23.supplement_s45</mixed-citation></citation-alternatives></ref><ref id="cit68"><label>68</label><citation-alternatives><mixed-citation xml:lang="ru">Namera A, Yashiki M, Okada K, Iwasaki Y, Kojima T. Rapid quantitative analysis of oleandrin in human blood by high-performance liquid chromatography. Nihon Hoizaku Zasshi. 1997;51(4):315–8. PMID: 9366138</mixed-citation><mixed-citation xml:lang="en">Namera A, Yashiki M, Okada K, Iwasaki Y, Kojima T. Rapid quantitative analysis of oleandrin in human blood by high-performance liquid chromatography. Nihon Hoizaku Zasshi. 1997;51(4):315–8. PMID: 9366138</mixed-citation></citation-alternatives></ref><ref id="cit69"><label>69</label><citation-alternatives><mixed-citation xml:lang="ru">Desta B. HPLC analysis of digoxin and digitoxin: development of methods for dosage form assay and separation of potential impurities and metabolites. University of British Columbia; 1982. https://doi.org/10.14288/1.0095102</mixed-citation><mixed-citation xml:lang="en">Desta B. HPLC analysis of digoxin and digitoxin: development of methods for dosage form assay and separation of potential impurities and metabolites. University of British Columbia; 1982. https://doi.org/10.14288/1.0095102</mixed-citation></citation-alternatives></ref><ref id="cit70"><label>70</label><citation-alternatives><mixed-citation xml:lang="ru">Pérez-Alonso N, Martín R, Capote A, Pérez A, Hernández-Díaz EK, Rojas L, et al. Efficient direct shoot organogenesis, genetic stability and secondary metabolite production of micropropagated Digitalis purpurea L. Ind Crops Prod. 2018;116:259–66. https://doi.org/10.1016/j.indcrop.2018.02.067</mixed-citation><mixed-citation xml:lang="en">Pérez-Alonso N, Martín R, Capote A, Pérez A, Hernández-Díaz EK, Rojas L, et al. Efficient direct shoot organogenesis, genetic stability and secondary metabolite production of micropropagated Digitalis purpurea L. Ind Crops Prod. 2018;116:259–66. https://doi.org/10.1016/j.indcrop.2018.02.067</mixed-citation></citation-alternatives></ref><ref id="cit71"><label>71</label><citation-alternatives><mixed-citation xml:lang="ru">Hensel A, Kreis W. GLC-MS investigations on cardenolide genins. Pharm Acta Helv. 1997;72(4):243–6. https://doi.org/10.1016/S0031-6865(97)00020-4</mixed-citation><mixed-citation xml:lang="en">Hensel A, Kreis W. GLC-MS investigations on cardenolide genins. Pharm Acta Helv. 1997;72(4):243–6. https://doi.org/10.1016/S0031-6865(97)00020-4</mixed-citation></citation-alternatives></ref><ref id="cit72"><label>72</label><citation-alternatives><mixed-citation xml:lang="ru">Платонов ВВ, Волочаева МВ, Хадарцев АА, Мелякова ДА, Сухих ГТ, Дунаева ИВ. Химический состав этанольного экстракта ландыша майского (Convallaria majalis L., семейство лилейных). Вестник новых медицинских технологий. 2019;(2):53–60. https://doi.org/10.24411/1609-2163-2019-16356</mixed-citation><mixed-citation xml:lang="en">Platonov VV, Volochaeva MV, Khadartsev AA, Melyakova DA, Sukhikh GT, Dunaeva IV. The chemical composition of ethanol extract of lily of the valley (Convallaria majalis L., Lily family). Journal of New Medical Technologies. 2019;(2):53–60 (In Russ.). https://doi.org/10.24411/1609-2163-2019-16356</mixed-citation></citation-alternatives></ref><ref id="cit73"><label>73</label><citation-alternatives><mixed-citation xml:lang="ru">Быков ЕВ, Вихарева ЕВ. Фармакопейные методы анализа сердечных гликозидов в растительном сырье и лекарственных препаратах (обзор). Вопросы биологической, медицинской и фармацевтической химии. 2023;26(7):5–11. https://doi.org/10.29296/25877313-2023-07-01</mixed-citation><mixed-citation xml:lang="en">Bykov EV, Vikhareva EV. Pharmacopoeial methods for the analysis of cardiac glycosides in plant raw materials and medicines (review). Problems of Biological, Medical and Pharmaceutical Chemistry. 2023;26(7):5–11 (In Russ.). https://doi.org/10.29296/25877313-2023-07-01</mixed-citation></citation-alternatives></ref><ref id="cit74"><label>74</label><citation-alternatives><mixed-citation xml:lang="ru">Орынбекова СО, Келеке АС, Сакипова ЗБ, Ибрагимова ЛН, Сермухамедова ОВ, Нургожин ТС. Сравнительная оценка методик идентификации сердечных гликозидов в лекарственном растительном сырье. Вестник Казахского Национального медицинского университета. 2019;(2):396–9.</mixed-citation><mixed-citation xml:lang="en">Orynbekova SO, Keleke AS, Sakipova ZB, Ibragimova LN, Sermukhamedova OV, Nurgozhin TS. Comparative evaluation of the identification methods of cardiac glycosides in herbal drugs. Vestnik KazNMU. 2019;(2):396–9 (In Russ.).</mixed-citation></citation-alternatives></ref></ref-list><fn-group><fn fn-type="conflict"><p>The authors declare that there are no conflicts of interest present.</p></fn></fn-group></back></article>
