Preparation of Bisoprolol Impurity A of High Quality | Chapter 7 | Theory and Applications of Chemistry Vol. 2
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.
Author(s) Details
Elżbieta Dąbrowska-Maś
ICN Polfa Rzeszów S.A., 35-959 Przemyslowa 2, Poland.
ICN Polfa Rzeszów S.A., 35-959 Przemyslowa 2, Poland.
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