Rapid Raman Spectroscopic Analysis of Stress Induced Degradation of the Pharmaceutical Drug Tetracycline

Domes Christian; Frosch Timea; Popp Juergen; Torsten Frosch

doi:10.3390/molecules25081866

Rapid Raman Spectroscopic Analysis of Stress Induced Degradation of the Pharmaceutical Drug Tetracycline

Molecules. 2020 Apr 17;25(8):1866. doi: 10.3390/molecules25081866.

Authors

Domes Christian¹, Frosch Timea¹, Popp Juergen^{1

2

3}, Torsten Frosch^{1

2

3}

Affiliations

¹ Leibniz Institute of Photonic Technology, 07745 Jena, Germany.
² Institute of Physical Chemistry, Friedrich Schiller University, 07743 Jena, Germany.
³ Abbe Center of Photonics, Friedrich Schiller University, 07745 Jena, Germany.

Abstract

Stress factors caused by inadequate storage can induce the unwanted degradation of active compounds in pharmaceutical formulations. Resonance Raman spectroscopy is presented as an analytical tool for rapid monitoring of small concentration changes of tetracycline and the metabolite 4-epianhydrotetracycline. These degradation processes were experimentally induced by changes in temperature, humidity, and irradiation with visible light over a time period of up to 23 days. The excitation wavelength λ_exc = 413 nm was proven to provide short acquisition times for the simultaneous Raman spectroscopic detection of the degradation of tetracycline and production of its impurity in small sample volumes. Small concentration changes could be detected (down to 1.4% for tetracycline and 0.3% for 4-epianhydrotetracycline), which shows the potential of resonance Raman spectroscopy for analyzing the decomposition of pharmaceutical products.

Keywords: active pharmaceutical ingredients; antibiotics; decomposition of pharmaceutical products; drug degradation; drug monitoring; resonance Raman spectroscopy; storage stress test.

MeSH terms

Density Functional Theory
Drug Monitoring
Inactivation, Metabolic*
Models, Molecular
Molecular Conformation
Molecular Structure
Spectrum Analysis
Spectrum Analysis, Raman* / methods
Stress, Physiological* / drug effects
Tetracycline / chemistry
Tetracycline / metabolism*
Tetracycline / pharmacokinetics

Substances

Tetracycline