vedomostiregmedРегуляторные исследования и экспертиза лекарственных средствRegulatory Research and Medicine Evaluation3034-30623034-3453Federal State Budgetary Institution ‘Scientific Centre for Expert Evaluation of Medicinal Products’ of the Ministry of Health of the Russian Federation (FSBI ‘SCEEMP’)10.30895/1991-2919-2022-12-1-24-40vedomostiregmed-405Research ArticleГлавная тема: Спектральные методы анализа в экспертизе лекарственных средствMAIN TOPIC: SPECTROSCOPIC METHODS USED IN MEDICINE EVALUATIONПрименение метода диффузионно-упорядоченной спектроскопии ЯМР для анализа полисахаридовDiffusion-Ordered NMR Spectroscopy Application for Analysis of Polysaccharideshttps://orcid.org/0000-0002-9133-0835КузьминаН. Е.Kuz’minaN. E.

Кузьмина Наталия Евгеньевна, доктор химических наук

Петровский б-р, д. 8, стр. 2, Москва, 127051

Natalia E. Kuz’mina, Dr. Sci. (Chem.)

8/2 Petrovsky Blvd, Moscow 127051

KuzminaN@expmed.ruhttps://orcid.org/0000-0003-1310-4477МоисеевС. В.MoiseevS. V.

Моисеев Сергей Владимирович, кандидат химических наук, доцент

Петровский б-р, д. 8, стр. 2, Москва, 127051

Sergey V. Moiseev, Cand. Sci. (Chem.), Assistant Professor

8/2 Petrovsky Blvd, Moscow 127051

MoiseevSV@expmed.ruhttps://orcid.org/0000-0001-5695-8048СевериноваЕ. Ю.SeverinovaE. Yu.

Северинова Елена Юрьевна

Петровский б-р, д. 8, стр. 2, Москва, 127051

Elena Yu. Severinova

8/2 Petrovsky Blvd, Moscow 127051

Severinova@expmed.ruhttps://orcid.org/0000-0001-8752-5245ЛутцеваА. И.LuttsevaA. I.

Лутцева Анна Ивановна, кандидат фармацевтических наук

Петровский б-р, д. 8, стр. 2, Москва, 127051

Anna I. Luttseva, Cand. Sci. (Pharm.)

8/2 Petrovsky Blvd, Moscow 127051

Lutceva@expmed.ruФедеральное государственное бюджетное учреждение «Научный центр экспертизы средств медицинского применения» Министерства здравоохранения Российской ФедерацииРоссияScientific Centre for Expert Evaluation of Medicinal ProductsRussian Federation2022210220221212440Copyright © Кузьмина Н.Е., Моисеев С.В., Северинова Е.Ю., Лутцева А.И., 20222022Кузьмина Н.Е., Моисеев С.В., Северинова Е.Ю., Лутцева А.И.Kuz’mina N.E., Moiseev S.V., Severinova E.Y., Luttseva A.I.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.vedomostincesmp.ru/jour/article/view/405

Метод диффузионно-упорядоченной спектроскопии ядерного магнитного резонанса (DOSY) является разновидностью транспортных методов, используемых в аналитической химии. Он основан на экспериментальном фиксировании трансляционной подвижности молекул при термодинамическом равновесии в  растворе, которая количественно характеризуется коэффициентом самодиффузии. Цель работы — обобщение основных направлений использования метода DOSY для анализа природных и модифицированных природных полисахаридов, применяемых в фармацевтике и фармацевтической биотехнологии. В обзоре показано, что этот метод является действенным инструментом для мониторинга фракционирования при выделении полисахаридов из природной смеси, оценки их средней молекулярной массы и молекулярно-массового распределения, изучения образования супрамолекулярных систем на основе полисахаридов. Описаны основные проблемы прецизионного измерения коэффициента самодиффузии макромолекул полисахаридов, приведены поправочные коэффициенты для нивелирования ошибок, связанных с колебаниями температуры и вязкости растворов. С помощью понятия полифазности дано объяснение экспериментально наблюдаемому разбросу значений коэффициентов самодиффузии ядер макромолекулы узкодисперсного полимера. Показаны способы характеристики трансляционной подвижности полифазной полимерной макромолекулы как единого целого. Обобщены значения параметров импульсных градиентных последовательностей, используемых при количественных измерениях коэффициентов самодиффузии линейных, малоразветвленных и разветвленных полисахаридов.

Diffusion-ordered nuclear magnetic resonance spectroscopy (DOSY) is a molecular transport method in analytical chemistry, based on experimental recording of the molecules’ translational mobility at thermodinamic equilibrium in a solution. The translational mobility is characterised quantitatively by a self-diffusion coefficient. The aim of the study was to summarise the main trends in application of DOSY for the analysis of natural and modified natural polysaccharides used in pharmaceuticals and pharmaceutical biotechnology. The review shows that this method is an effective instrument for monitoring fractionation during isolation of polysaccharides from a natural mixture, for estimating their average molecular weight and molecular weight distribution, and for studying the formation of supramolecular systems based on polysaccharides. The paper describes main issues of the precise measurement of polysaccharide macromolecules self-diffusion coefficients and provides the correction factors to compensate for errors caused by fluctuations in temperature and viscosity of solutions. The observed scatter of self-diffusion coefficients of narrowly dispersed polymer macromolecules nuclei is explained using the polyphase concept. The paper illustrates ways of describing translational mobility of a polyphase polymer macromolecule as a whole. The authors summarise values of the gradient pulse sequence parameters used in quantitative measurements of self-diffusion coefficients of linear, low-branched, and branched polysaccharides.

 

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