pharmjournalРазработка и регистрация лекарственных средствDrug development & registration2305-20662658-5049LLC «CPHA»10.33380/2305-2066-2023-12-1-227-236pharmjournal-1453Research ArticleРЕГУЛЯТОРНЫЕ ВОПРОСЫREGULATORY ISSUESОб аналитических и технологических причинах результатов Out-of-Specification для тестов количественное определение и растворение (обзор)About Analytical and Technological Reasons of Out-of-Specification Results for Assay and Disolution Tests (Review)https://orcid.org/0000-0001-8047-4078ЭпштейнН. А.EpshteinN. A.

115446, г. Москва, Коломенский проезд, 13А

13A, Kolomensky passage, Moscow, 115446

naumepshtein@gmail.comЦентр регистрации и разработки лекарственных средств ООО «ИРВИН 2»Center of registration and development of medicines LLC «IRVIN 2»202328022023121227236Copyright © Эпштейн Н.А., 20232023Эпштейн Н.А.Epshtein N.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.pharmjournal.ru/jour/article/view/1453Введение

Введение. Результаты вне спецификации (OOS results) представляют собой серьезную проблему при разработке, валидации и использовании методик «Количественное определение» и «Растворение». Тема актуальная, что подтверждается данными поиска в Internet по фразе «Out-of-Specification» + «HPLC» – найдено около 35 300 результатов.

Текст

Текст. Рассмотрены и систематизированы в виде сводной таблицы важные для практики аналитические и технологические причины (факторы), которые могут приводить к получению заниженных или завышенных результатов анализов. Речь идет о следующих факторах. Факторы, связанные с расчетной формулой. Факторы, связанные с подготовкой проб (образцов). Факторы, связанные с растворителем образца и соотношением pH раствора образца и подвижной фазы. Факторы, связанные с хроматограммами и их обработкой. Основные технологические факторы.

Заключение

Заключение. Представлены данные и рекомендации для поиска аналитических и технологических причин получения результатов Out-of-Specification в случае тестов «Количественное определение» и «Растворение».

Introduction

Introduction. Out of specification (OOS) results represent a major challenge in the development, validation and use of the Assay and Dissolution methods. The topic is relevant, which is confirmed by Internet search data for the phrase "Out-of-Specification" + "HPLC" – about 35,300 results were found.

Text

Text. The analytical and technological reasons (factors) that can lead to underestimated or overestimated test results are considered and systematized in the form of a summary table important for practice. These are the following factors. Factors associated with the calculation formula. Factors related to the preparation of samples. Factors related to the sample solvent and ratio of the pH the sample solution and the mobile phase. Factors associated with chromatograms and their processing. The main technological factors.

Conclusion

Conclusion. Data and recommendations are presented to search for analytical and technological reasons for obtaining Out-of-Specification results in the case of tests Assay and Dissolution.

Out-of-Specificationпричиныаналитические и технологические факторытест «Количественное определение»тест «Растворение»Out-of-Specificationreasonsanalytical and technological factorsReferencesGuidance for Industry. Investigating Out-of-Specification (OOS). Test Results for Pharmaceutical Production. Revision 1. Rockville: FDA; 2022.Guidance for Industry. Investigating Out-of-Specification (OOS). Test Results for Pharmaceutical Production. Revision 1. Rockville: FDA; 2022.Kelly B. Anderson. Out-of-Specification (OOS) Investigations. Avoiding Complete Failure by Looking at All Pieces of the Puzzle. New York: John Wiley and Sons Ltd.; 2018.Kelly B. Anderson. Out-of-Specification (OOS) Investigations. Avoiding Complete Failure by Looking at All Pieces of the Puzzle. New York: John Wiley and Sons Ltd.; 2018.Thomas S., Huynh-Ba K. Highlights of Investigating Out-of-Specifications Test Results. Pharmaceutical Stability Testing to Support Global Markets. 2010;229–237. DOI: 10.1007/978-1-4419-0889-6_28Thomas S., Huynh-Ba K. Highlights of Investigating Out-of-Specifications Test Results. Pharmaceutical Stability Testing to Support Global Markets. 2010;229–237. DOI: 10.1007/978-1-4419-0889-6_28Kuselman I., Pennecchi F., Burns C., Fajgelj A., de Zorzi P. IUPAC/CITAC Guide: Investigating out-of-specification test results of chemical composition based on metrological concepts (IUPAC Technical Report). Pure and Applied Chemistry. 2012;84(9):1939–1971. DOI: 10.1351/PAC-REP-11-10-04.Kuselman I., Pennecchi F., Burns C., Fajgelj A., de Zorzi P. IUPAC/CITAC Guide: Investigating out-of-specification test results of chemical composition based on metrological concepts (IUPAC Technical Report). Pure and Applied Chemistry. 2012;84(9):1939–1971. DOI: 10.1351/PAC-REP-11-10-04.Kumar K. A., Gupta N. V. Handling of Out of Specification Results. Intern. International Journal of Pharmaceutical Quality Assurance. 2015;6(2);38–44.Kumar K. A., Gupta N. V. Handling of Out of Specification Results. Intern. International Journal of Pharmaceutical Quality Assurance. 2015;6(2);38–44.Hemanth K. S., Paneesh C. Handling Out-of-Specification during laboratory incidence. J. Global Trends Pharm. Sci. 2019;10(3):6591–6597.Hemanth K. S., Paneesh C. Handling Out-of-Specification during laboratory incidence. J. Global Trends Pharm. Sci. 2019;10(3):6591–6597.McDowall R. D. Are You Invalidating Out-of-Specification (OOS) Results into Compliance? LCGC North America. 2020;37(7):411–419.McDowall R. D. Are You Invalidating Out-of-Specification (OOS) Results into Compliance? LCGC North America. 2020;37(7):411–419.Mote N. N. Reference for Investigation of Out of Specification Results in Pharmaceutical Industry. Austin Pharmacology & Pharmaceutics. 2021;6(1):01–07.Mote N. N. Reference for Investigation of Out of Specification Results in Pharmaceutical Industry. Austin Pharmacology & Pharmaceutics. 2021;6(1):01–07.Köppel H., Schneider B., Wätzig H. Out-of-specification test results from the statistical point of view. Journal of Pharmaceutical and Biomedical Analysis. 2007;44(3):718–729. DOI: 10.1016/j.jpba.2007.02.035Köppel H., Schneider B., Wätzig H. Out-of-specification test results from the statistical point of view. Journal of Pharmaceutical and Biomedical Analysis. 2007;44(3):718–729. DOI: 10.1016/j.jpba.2007.02.035.Эпштейн Н. А. Аттестация фармацевтических субстанций как лабораторных первичных стандартов (обзор). Химико-фармацевтический журнал. 2021;55(6):47–52. DOI: 10.30906/0023-1134-2021-55-6-47-52.Epshtein N. A. Certification of Pharmaceutical Substances as In-House Primary Standards (Review). Khimiko-Farmatsevticheskii Zhurnal. 2021;55(6):47–52. (In Russ.) DOI: 10.30906/0023-1134-2021-55-6-47-52.Epshtein N. A. Certification of pharmaceutical substances as in-house primary standards (Review). Pharm. Chem. J. 2021;55(6):616–620. DOI: 10.1007/s11094-021-02466-1.Epshtein N. A. Certification of pharmaceutical substances as in-house primary standards (Review). Pharm. Chem. J. 2021;55(6):616–620. DOI: 10.1007/s11094-021-02466-1.Эпштейн Н. А. Тест «растворение»: причины получения заниженных результатов и их устранение (Обзор). Химико-фармацевтический журнал. 2021;55(8):55–59. DOI: 10.30906/0023-1134-2021-55-8-55-59.Epshtein N. A. Dissolution Test: Causes of Understated Results and Elimination of These (Overview). Pharmaceutical Chemistry Journal. 2021;55(8):55–59. (In Russ.) DOI: 10.30906/0023-1134-2021-55-8-55-59.Snyder L. R., Kirkland J. J., Glajch J. L. Introduction to modern liquid chromatography. 3d ed. Hoboken, New Jersey: John Wiley and Sons.; 2010.Snyder L. R., Kirkland J. J., Glajch J. L. Introduction to modern liquid chromatography. 3d ed. Hoboken, New Jersey: John Wiley and Sons.; 2010.Эпштейн Н. А. Валидация хроматографических методик: контроль чистоты пиков и специфичности методик с использованием диодно-матричных детекторов (Обзор). Разработка и регистрация лекарственных средств. 2020;9(3):129–136. DOI: 10.33380/2305-2066-2020-9-3-129-136.Epshtein N. A. Validation of Chromatographic Methods: Checking the Peak Purity and the Specificity of Methods with Diode Array Detectors (Review). Drug development & registration. 2020;9(3):129–136. (In Russ.) DOI: 10.33380/2305-2066-2020-9-3-129-136.Bharate S. S., Bharate S. B., Bajajc A. N. Interactions and incompatibilities of pharmaceutical excipients with active pharmaceutical ingredients: a comprehensive review. J. Excipients and Food Chem. 2010;1(3):3–26.Bharate S. S., Bharate S. B., Bajajc A. N. Interactions and incompatibilities of pharmaceutical excipients with active pharmaceutical ingredients: a comprehensive review. J. Excipients and Food Chem. 2010;1(3):3–26.Hotha K. K., Roychowdhury S., Subramanian V. Drug-Excipient Interactions: Case Studies and Overview of Drug Degradation Pathways. Amer. J. Anal. Chem. 2016;7(01):107–140. DOI: 10.4236/ajac.2016.71011.Hotha K. K., Roychowdhury S., Subramanian V. Drug-Excipient Interactions: Case Studies and Overview of Drug Degradation Pathways. Amer. J. Anal. Chem. 2016;7(01):107–140. DOI: 10.4236/ajac.2016.71011.

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