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Synthesis of potential impurities of loteprednol etabonate and methods for chemical purity determination

Tomasz Giller 1Agnieszka Stopa Aleksandra Groman 1Wojciech J. Szczepek 1Katarzyna Badowska 

1. Pharmaceutical Research Institute (IF), Rydygiera 8, Warszawa 01-793, Poland


Loteprednol etabonate (LE, chloromethyl 17α-ethoxycarbonyloxy-11β-hydroxy-3-oxoandrosta-1,4-diene-17β-carboxylate, Fig. 1), a soft corticosteroid antiinflammatory drug was developed for topical use. It is derived from the inactive metabolite of prednisolone, i.e. 11β,17α-dihydroxy-3-oxoandrosta-1,4-diene-17β-carboxylic acid, by introduction of a chloromethyl ester to the 17β-position and ethylcarbonate ester to the 17α-position.

Fig. 1. Loteprednol etabonate.

Depending on the reaction sequences, reagents, reaction conditions as well as a substrate used in the synthesis of LE the final product (active pharmaceutical ingredient) is accompanied by different contaminants. Therefore, to evaluate purity of LE, we have synthesized eight compounds being potential process impurities or degradation products. Moreover, two additional process-impurities were isolated from the laboratory batches of LE by chromatographic methods. All these compounds were fully characterized by FT-IR, 1H and 13C NMR techniques.
Finally, UPLC analytical methods have been developed to assess the quality and safety of the final LE product. These methods have been also initially evaluated regarding their suitability for the intended purpose.

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Related papers

Presentation: Poster at VIII Multidyscyplinarna Konferencja Nauki o Leku, by Tomasz Giller
See On-line Journal of VIII Multidyscyplinarna Konferencja Nauki o Leku

Submitted: 2012-03-30 08:12
Revised:   2012-04-05 08:07