Pharmaceutical products quality control: modern methods for determination of ethylene and diethylene glycol impurities

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Abstract

Ethylene glycol (EG) and diethylene glycol (DEG) are toxic compounds that, when ingested, even in small amounts, cause severe systemic damage, including metabolic acidosis, acute kidney failure, neurological disorders, and other life-threatening conditions. These compounds pose a particular danger to children, as evidenced by numerous cases of mass poisonings from medicines contaminated with EG and DEG, reported globally in recent years. The presence of glycols in medicines results from the adulteration of excipients or the use of substandard ethoxylated substances. In response to recent poisoning incidents, regulatory agencies worldwide have tightened standards, setting a maximum allowable limit of 0.1% for each contaminant. In connection with the current situation, it becomes obvious that rigorous quality control of both excipients and finished products is necessary for the presence of dangerous impurities of EG and DEG. This article reviews and compares modern analytical methods for EG and DEG detection in medicines, focusing on three widely adopted and officially approved techniques:

  • Thin-Layer Chromatography (TLC) – a simple and cost-effective method used primarily for screening studies;
  • Gas Chromatography with Flame Ionization Detection (GC-FID) – the most accurate and reliable method recommended by WHO and the world's leading pharmacopoeias;
  • High Performance Liquid Chromatography with Refractive Index Detection (HPLC-RID) – an alternative method that complements existing approaches.

Aspects of the application of each of these methods, including sample preparation and chromatographic separation parameters, are considered. Attention is also paid to the interfering effect of excipients on the analysis results and the need to adapt techniques for each drug.

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About the authors

N. G. Paskar

I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation

Author for correspondence.
Email: nnikpaskar@yandex.ru
ORCID iD: 0009-0002-6656-6667
SPIN-code: 8269-0440

Student of the A.P. Nelyubin Institute of Pharmacy

Russian Federation, 8/2, Trubetskaya str., Moscow, 119991

N. V. Pyatigorskaya

I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation

Email: pyatigorskaya_n_v@staff.sechenov.ru
ORCID iD: 0000-0003-4901-4625
SPIN-code: 8128-1725

Ph.D. (Pharm.), Professor, Corresponding Member of the RAS, Head of the Department of Industrial Pharmacy

Russian Federation, 8/2, Trubetskaya str., Moscow, 119991

Е. О. Bakhrushina

I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation

Email: bakhrushina_e_o@staff.sechenov.ru
ORCID iD: 0000-0001-8695-0346
SPIN-code: 9537-1297

Ph.D. (Pharm.), Associate Professor at the Department of Pharmaceutical Technology

Russian Federation, 8/2, Trubetskaya str., Moscow, 119991

S. P. Senchenko

Research and Testing Center “FARMOBORONA” LLC

Email: senchenko_sergey@farmoborona.ru
ORCID iD: 0000-0003-0212-3840
SPIN-code: 4860-0144

Ph.D. (Pharm.), Associate Professor, Head of the Department for Development of Analytical Methods

Russian Federation, 46A, Gagarina str., Korolev, Moscow region, 141074

T. V. Potupchik

Federal State Budgetary Educational Institution of Higher Education “Prof. V.F. Voino-Yasenetsky Krasnoyarsk State Medical University” of the Ministry of Health of the Russian Federation

Email: potupchik_tatyana@mail.ru
ORCID iD: 0000-0003-1133-4447
SPIN-code: 8353-3513

Ph.D. (Med.), Associate Professor of the Department of Pharmacology and Clinical Pharmacology with a postgraduate course

Russian Federation, Partizan Zheleznyak str., Krasnoyarsk, 660022

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