Preparation of Bisoprolol Impurity A of High Quality

Aims: Research on the convenient method for obtaining (RS)-1-(4-Hydroxymethyl-phenoxy)-3-isopropylaminopropan-2-ol, known as the Impurity A of Bisoprolol according to EP, of high quality.

Study Design: Impurity A may be formed as a by-product in the common processes used for synthesis of bisoprolol fumarate. Impurity A may be also formed as a result of degradation (hydrolysis) of Bisoprolol. This chemical compound is available as the reference standard, but the offered purity is between 95% and 97%, what suggest that its purification to high quality is demanding. The most common method used for purification of chemical standards is preparative chromatography, but it is unattainable in many cases. There is continuous need for simple, convenient and repeatable laboratory procedures.

Methodology: The synthesis of Bisoprolol Impurity A was performed starting from p-hydroxybenzyl alcohol and subsequent reactions with epichlorohydrin and is opropylamine. Purification process consisted particularly onobtaining and isolation of fumarate salt of Impurity A, its crystallization and subsequent basification.

Results: The reference standard of Bisoprolol Impurity A of 95.5% purity was obtained with convenient purification process. The structure of Impurity A was elucidated with IR, NMR and EA and its purity was determined by HPLC technique.

Conclusion: The effective method of preparation of Impurity A of high qualityis described in this paper.

For more information contact author

Elżbieta Dąbrowska-Maś
ICN Polfa Rzeszów S.A., 35-959 Przemyslowa 2, Poland.
E-mail: Elzbieta.DabrowskaMas@valeant.com

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