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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">scbmt</journal-id><journal-title-group><journal-title xml:lang="ru">БИОМЕДИЦИНА</journal-title><trans-title-group xml:lang="en"><trans-title>Journal Biomed</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">2074-5982</issn><issn pub-type="epub">2713-0428</issn><publisher><publisher-name>Scientific center of biomedical technologies of Federal Medical and Biological Agency</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.33647/2074-5982-21-4-49-53</article-id><article-id custom-type="elpub" pub-id-type="custom">scbmt-1794</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>МЕТОДЫ И ТЕХНОЛОГИИ БИОМЕДИЦИНСКИХ ИССЛЕДОВАНИЙ</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>METHODS AND TECHNOLOGIES OF BIOMEDICAL RESEARCH</subject></subj-group></article-categories><title-group><article-title>Исследование матричного эффекта при метаболомном анализе маркеров хронической болезни почек в моче методом гидрофильной хроматографии с масс-спектрометрическим детектированием</article-title><trans-title-group xml:lang="en"><trans-title>Study of Matrix Effect in Metabolomic Analysis of Urinary Markers of Chronic Kidney Disease by Hydrophilic Interaction Chromatography Tandem Mass Spectrometry</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Данилова</surname><given-names>Е. Ю.</given-names></name><name name-style="western" xml:lang="en"><surname>Danilova</surname><given-names>E. Yu.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Данилова Елена Юрьевна</p><p>119991, Москва, тер. Ленинские Горы, 1, стр. 3</p><p>119048, Москва, ул. Трубецкая, 8, стр. 2</p></bio><bio xml:lang="en"><p>Elena Yu. Danilova</p><p>119991, Moscow, Leninskie Gory, 1, Build. 3</p><p>119048, Moscow, Trubetskaya Str., 8, Build. 2</p></bio><email xlink:type="simple">phenolyat@gmail.com</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Ерощенко</surname><given-names>Н. Н.</given-names></name><name name-style="western" xml:lang="en"><surname>Eroshchenko</surname><given-names>N. N.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Ерощенко Николай Николаевич</p><p>119048, Москва, ул. Трубецкая, 8, стр. 2</p></bio><bio xml:lang="en"><p>Nikolay N. Eroshchenko</p><p>119048, Moscow, Trubetskaya Str., 8, Build. 2</p></bio><email xlink:type="simple">nikolay.eroshchenko@yandex.ru</email><xref ref-type="aff" rid="aff-2"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Морозова</surname><given-names>О. Л.</given-names></name><name name-style="western" xml:lang="en"><surname>Morozova</surname><given-names>O. L.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Морозова Ольга Леонидовна, д.м.н., проф.</p><p>119048, Москва, ул. Трубецкая, 8, стр. 2</p></bio><bio xml:lang="en"><p>Olga L. Morozova, Dr. Sci. (Med.), Prof.</p><p>119048, Moscow, Trubetskaya Str., 8, Build. 2</p></bio><email xlink:type="simple">morozova_o_l@staff.sechenov.ru</email><xref ref-type="aff" rid="aff-2"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Ставрианиди</surname><given-names>А. Н.</given-names></name><name name-style="western" xml:lang="en"><surname>Stavrianidi</surname><given-names>A. N.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Ставрианиди Андрей Николаевич, д.х.н., проф.</p><p>119991, Москва, тер. Ленинские Горы, 1, стр. 3</p></bio><bio xml:lang="en"><p>Andrey N. Stavrianidi, Dr. Sci. (Chem.), Prof.</p><p>119991, Moscow, Leninskie Gory, 1, Build. 3</p></bio><email xlink:type="simple">stavrianidi.andrey@gmail.com</email><xref ref-type="aff" rid="aff-3"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>ФГБОУ ВО «Московский государственный университет имени М.В. Ломоносова»; ФГАОУ ВО «Первый Московский государственный медицинский университет им. И.М. Сеченова» Минздрава России (Сеченовский университет)</institution><country>Россия</country></aff><aff xml:lang="en"><institution>M.V. Lomonosov Moscow State University; I.M. Sechenov First Moscow State Medical University of the Ministry of Health Care of Russia (Sechenov University)</institution><country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-2"><aff xml:lang="ru"><institution>ФГАОУ ВО «Первый Московский государственный медицинский университет им. И.М. Сеченова» Минздрава России (Сеченовский университет)</institution><country>Россия</country></aff><aff xml:lang="en"><institution>I.M. Sechenov First Moscow State Medical University of the Ministry of Health Care of Russia (Sechenov University)</institution><country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-3"><aff xml:lang="ru"><institution>ФГБОУ ВО «Московский государственный университет имени М.В. Ломоносова»</institution><country>Россия</country></aff><aff xml:lang="en"><institution>M.V. Lomonosov Moscow State University</institution><country>Russian Federation</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2025</year></pub-date><pub-date pub-type="epub"><day>18</day><month>12</month><year>2025</year></pub-date><volume>21</volume><issue>4</issue><fpage>49</fpage><lpage>53</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Данилова Е.Ю., Ерощенко Н.Н., Морозова О.Л., Ставрианиди А.Н., 2025</copyright-statement><copyright-year>2025</copyright-year><copyright-holder xml:lang="ru">Данилова Е.Ю., Ерощенко Н.Н., Морозова О.Л., Ставрианиди А.Н.</copyright-holder><copyright-holder xml:lang="en">Danilova E.Y., Eroshchenko N.N., Morozova O.L., Stavrianidi A.N.</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://journal.scbmt.ru/jour/article/view/1794">https://journal.scbmt.ru/jour/article/view/1794</self-uri><abstract><p>Метаболомный анализ биологических образцов является актуальным направлением развития методов диагностики хронической болезни почек (ХБП) у детей. Наиболее часто в метаболомике применяется метод гидрофильной хроматографии с масс-спектрометрическим детектированием (ГИХ-МС/МС), распространенной проблемой при использовании которого является матричный эффект. В рамках исследования была проведена оценка матричного эффекта (МЭ), возникающего при проведении анализа 9 низкомолекулярных полярных маркерных метаболитов ХБП в условиях гидрофильной хроматографии в образцах новой модельной мочи и реального образца. В качестве определяемых 9 биомаркеров были выбраны аминокислоты, их полярные метаболиты, участвующие в патофизиологических процессах развития хронической болезни почек. Оценка матричного эффекта на первом квадруполе проводилась методом расчета отношения параметров коэлюирования низкомолекулярных кластеров, состоящих из формиат-анионов буфера и катионов солей, входящих в состав мочи, и стандарта Л-валина-13C5. В реальной моче интенсивность сигнала стандарта Л-валина-13C5 снижалась более чем на 50% относительно метанола при наложении сигнала кластера, тогда как в искусственной моче эффект подавления был сравним с реальным образцом во всех условиях элюирования. Также был применен метод добавок для оценки МЭ не меченных изотопами эндогенных маркеров в реальной и искусственной матрицах. Показано, что предварительная оценка тушения сигнала может быть изучена на модельной моче нового состава. Полученные результаты демонстрируют важность оценки оптимального разрешения сигнала не только маркерных соединений, но и неорганических кластеров, что может существенно снизить погрешности анализа в условиях реальной матрицы. Оценка этого эффекта должна повысить точность анализа полярных метаболитов в реальных образцах в метаболомике ХБП. Примененные образцы искусственной мочи показали сопоставимый МЭ с реальным образцом, что подтверждает ее перспективность для оптимизации условий анализа методом ГИХ-МС/МС.</p></abstract><trans-abstract xml:lang="en"><p>Metabolomic analysis of biological samples is an important direction in the development of diagnostic methods for chronic kidney disease (CKD) in children. Hydrophilic interaction chromatography tandem mass spectrometry (HILIC–MS/MS) is widely used in metabolomics; however, this method is associated with the problem of matrix effect (ME). In this study, we evaluate the ME arising from the analysis of nine low-molecular weight polar marker metabolites of CKD under HILIC conditions in samples of new model and real urine. Amino acids and their polar metabolites involved in the pathophysiologic processes of CKD development were selected as nine biomarkers to be determined. The ME on the first quadrupole was assessed by calculating the ratio of the coelution parameters of low-molecular weight clusters consisting of buffer formate anions and salt cations in urine and L-valine-13C5 standard. In real urine, the signal intensity of the L-valine-13C5 standard was reduced by more than 50% relative to methanol when the cluster signal was superimposed, whereas in artificial urine, the suppression effect was comparable to the real sample under all elution conditions. The addition method was also applied to evaluate the ME of isotope-labeled endogenous markers in real and artificial matrices. It was shown that a preliminary assessment of signal quenching can be studied on model urine of a new composition. The results demonstrate the importance of evaluating the optimal signal resolution of not only marker compounds but also inorganic clusters, which can significantly reduce the analysis errors under real matrix conditions. The evaluation of this effect should improve the accuracy of polar metabolite analysis in real samples in CKD metabolomics. The applied artificial urine samples showed comparable ME to the real sample, which confirms its promising potential for optimizing the HILIC–MS/MS analysis conditions.</p></trans-abstract><kwd-group xml:lang="ru"><kwd>хроническая болезнь почек</kwd><kwd>метаболомика</kwd><kwd>матричные эффекты</kwd><kwd>масс-спектрометрия</kwd></kwd-group><kwd-group xml:lang="en"><kwd>chronic kidney disease</kwd><kwd>metabolomics</kwd><kwd>matrix effects</kwd><kwd>mass spectrometry</kwd></kwd-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">Amoresano A., Pucci P. Mass Spectrometry in Metabolomics. 1st ed. Elsevier. 2022.</mixed-citation><mixed-citation xml:lang="en">Amoresano A., Pucci P. Mass Spectrometry in Metabolomics. 1st ed. Elsevier. 2022.</mixed-citation></citation-alternatives></ref><ref id="cit2"><label>2</label><citation-alternatives><mixed-citation xml:lang="ru">Danilova E.Y., Maslova A.O., Stavrianidi A.N., et al. CKD urine metabolomics: modern concepts and approaches. Pathophysiology. 2023;30. DOI: 10.3390/pathophysiology30040033.</mixed-citation><mixed-citation xml:lang="en">Danilova E.Y., Maslova A.O., Stavrianidi A.N., et al. CKD urine metabolomics: modern concepts and approaches. Pathophysiology. 2023;30. DOI: 10.3390/pathophysiology30040033.</mixed-citation></citation-alternatives></ref><ref id="cit3"><label>3</label><citation-alternatives><mixed-citation xml:lang="ru">Giskeødegård G.F., Andreassen T., Bertilsson H., et al. The effect of sampling procedures and day-to-day variations in metabolomics studies of biofluids. Anal. Chim. Acta. 2019;1081:93–102. DOI: 10.1016/j.aca.2019.07.026.</mixed-citation><mixed-citation xml:lang="en">Giskeødegård G.F., Andreassen T., Bertilsson H., et al. The effect of sampling procedures and day-to-day variations in metabolomics studies of biofluids. Anal. Chim. Acta. 2019;1081:93–102. DOI: 10.1016/j.aca.2019.07.026.</mixed-citation></citation-alternatives></ref><ref id="cit4"><label>4</label><citation-alternatives><mixed-citation xml:lang="ru">Glavan M.R., Socaciu C., Socaciu A.I., et al. Untargeted metabolomics by ultra-high-performance liquid chromatography coupled with electrospray ionization-quadrupole-time of flight-mass spectrometry analysis identifies a specific metabolomic profile in patients with early chronic kidney disease. Biomedicines. 2023;11(4):1057.DOI: 10.3390/biomedicines11041057.</mixed-citation><mixed-citation xml:lang="en">Glavan M.R., Socaciu C., Socaciu A.I., et al. Untargeted metabolomics by ultra-high-performance liquid chromatography coupled with electrospray ionization-quadrupole-time of flight-mass spectrometry analysis identifies a specific metabolomic profile in patients with early chronic kidney disease. Biomedicines. 2023;11(4):1057.DOI: 10.3390/biomedicines11041057.</mixed-citation></citation-alternatives></ref><ref id="cit5"><label>5</label><citation-alternatives><mixed-citation xml:lang="ru">Hocher B., Adamski J. Metabolomics for clinical use and research in chronic kidney disease. Nat. Rev. Nephrol. 2017;13:269–284. DOI: 10.1038/nrneph.2017.30.</mixed-citation><mixed-citation xml:lang="en">Hocher B., Adamski J. Metabolomics for clinical use and research in chronic kidney disease. Nat. Rev. Nephrol. 2017;13:269–284. DOI: 10.1038/nrneph.2017.30.</mixed-citation></citation-alternatives></ref><ref id="cit6"><label>6</label><citation-alternatives><mixed-citation xml:lang="ru">Khamis M.M., Adamko D.J., El-Aneed A. Mass spectrometric based approaches in urine metabolomics and biomarker discovery. Mass Spectrom. Rev. 2017;36:115–134. DOI: 10.1002/mas.21455.</mixed-citation><mixed-citation xml:lang="en">Khamis M.M., Adamko D.J., El-Aneed A. Mass spectrometric based approaches in urine metabolomics and biomarker discovery. Mass Spectrom. Rev. 2017;36:115–134. DOI: 10.1002/mas.21455.</mixed-citation></citation-alternatives></ref><ref id="cit7"><label>7</label><citation-alternatives><mixed-citation xml:lang="ru">Rysz J., Gluba-Brzózka A., Franczyk B., et al. Novel biomarkers in the diagnosis of chronic kidney disease and the prediction of its outcome. Int. J. Mol. Sci. 2017;18:1702. DOI: 10.3390/ijms18081702.</mixed-citation><mixed-citation xml:lang="en">Rysz J., Gluba-Brzózka A., Franczyk B., et al. Novel biomarkers in the diagnosis of chronic kidney disease and the prediction of its outcome. Int. J. Mol. Sci. 2017;18:1702. DOI: 10.3390/ijms18081702.</mixed-citation></citation-alternatives></ref><ref id="cit8"><label>8</label><citation-alternatives><mixed-citation xml:lang="ru">Sanchez-Niño M.D., Sanz A.B., Ramos A.M., et al. Clinical proteomics in kidney disease as an exponential technology: heading towards the disruptive phase. Clin. Kidney J. 2017;10:188–191. DOI: 10.1093/ckj/sfx023.</mixed-citation><mixed-citation xml:lang="en">Sanchez-Niño M.D., Sanz A.B., Ramos A.M., et al. Clinical proteomics in kidney disease as an exponential technology: heading towards the disruptive phase. Clin. Kidney J. 2017;10:188–191. DOI: 10.1093/ckj/sfx023.</mixed-citation></citation-alternatives></ref><ref id="cit9"><label>9</label><citation-alternatives><mixed-citation xml:lang="ru">Sarigul N., Korkmaz F., Kurultak İ. A new artificial urine protocol to better imitate human urine. Sci. Rep. 2019;9:1–11. DOI: 10.1038/s41598-019-56693-4.</mixed-citation><mixed-citation xml:lang="en">Sarigul N., Korkmaz F., Kurultak İ. A new artificial urine protocol to better imitate human urine. Sci. Rep. 2019;9:1–11. DOI: 10.1038/s41598-019-56693-4.</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>
