Substantiation of an approach to determination of ketoprofen macrogol 400 esters

Authors

DOI:

https://doi.org/10.15587/2519-4852.2021.235980

Keywords:

ketoprofen, macrogol 400, ester, impurity, chromatogram, absorption spectrum, molecular mass

Abstract

The aim. The work is concerned with the substantiation of the approach to the identification and quantitative determination of ketoprofen macrogol 400 esters.

Materials and methods. Ketoprofen, macrogol 400, ketoprofen macrogol 400 ester (KM400E), as well as model cream-gels were studied by the following methods: absorption spectrophotometry ultraviolet (UV) and visible, high-performance liquid chromatography (HPLC), gas chromatography (GC), GC / mass spectrometry, nuclear magnetic resonance (NMR) spectrometry and thermogravimetry.

Results. It was found by GC and GC / mass spectrometry that the average molecular mass (Mr) of the test macrogol 400 is 383.50 and it contains oligomers with molecular masses from 150.17 to 546.65. KM400E, which is a mixture of esters of ketoprofen with macrogol oligomers, was synthesized. The formed esters were characterized by 1H NMR spectra. It was shown that the ratio of the average molecular mass of KM400E, calculated for monoesters, and the molecular mass of ketoprofen corresponds to the ratio of specific absorbances of solutions of ketoprofen and solutions of KM400E, this fact indicated the formation of monoesters. Taking into account the risk of variability of the fractional composition of macrogol 400 in different batches, it is advisable to quantify KM400E using ketoprofen reference standard (RS) and not KM400E RS. Using HPLC with diode array detection the peak of KM400E should be identified by the UV absorption spectrum with λmax≈255 nm, which is characteristic for ketoprofen, and the relative retention time (RRt) of the peak; KM400E should be quantified by the content of ketoprofen in this impurity.

During storage of model cream-gels the content of KM400E impurity is significantly lower than the content of ketoprofen propylene glycol ester (mixture of isomers).

Conclusions. The approach to the identification and quantitative determination of KM400E is substantiated. The analytical procedure for determination of KM400E impurity by HPLC with a diode array detection using ketoprofen RS was developed. Correctness of the procedure was proved by the results of the validation studies.

Author Biographies

Elena Bezuglaya, State Scientific Institution “Institute for Single Crystals” of National Academy of Sciences of Ukraine

PhD, Senior Researcher, Head of Laboratory.

Laboratory of Technology and Analysis of Medicinal Products

Igor Zinchenko, State Scientific Institution “Institute for Single Crystals” of National Academy of Sciences of Ukraine

PhD, Junior Researcher

Laboratory of Technology and Analysis of Medicinal Products

Nikolay Lyapunov, State Scientific Institution “Institute for Single Crystals” of National Academy of Sciences of Ukraine

Doctor of Pharmaceutical Sciences, Professor, Leading Researcher

Laboratory of Technology and Analysis of Medicinal Products

Hanna Vlasenko, State Scientific Institution “Institute for Single Crystals” of National Academy of Sciences of Ukraine

PhD, Junior Researcher

Department of Luminescent Materials and Dyes

Vladimir Musatov, State Scientific Institution “Institute for Single Crystals” of National Academy of Sciences of Ukraine

PhD, Senior Researcher

Department of Organic and Bioorganic Chemistry

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Published

2021-06-30

How to Cite

Bezuglaya, E., Zinchenko, I., Lyapunov, N., Vlasenko, H., & Musatov, V. (2021). Substantiation of an approach to determination of ketoprofen macrogol 400 esters. ScienceRise: Pharmaceutical Science, (3(31), 51–63. https://doi.org/10.15587/2519-4852.2021.235980

Issue

No. 3(31) (2021)

Section

Pharmaceutical Science

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Copyright (c) 2021 Elena Bezuglaya, Igor Zinchenko, Nikolay Lyapunov, Hanna Vlasenko, Vladimir Musatov

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