Carry Over of Impurities: A Detailed Exemplification for Glycopyrrolate (NVA237)

The original synthesis of glycopyrrolate (NVA237) was revised and shortened into an essentially one-pot process. Without isolating the intermediates, their purification became obsolete, thereby increasing the possibility of the carry over of impurities. For that reason, the actual, potential, and th...

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Bibliographic Details
Published in:	Organic process research & development Vol. 16; no. 11; pp. 1754 - 1769
Main Authors:	Allmendinger, Thomas, Bixel, Dominique, Clarke, Adrian, Di Geronimo, Laura, Fredy, Jean-Wilfried, Manz, Marco, Gavioli, Elena, Wicky, Regine, Schneider, Martin, Stauffert, Fabien J, Tibi, Markus, Valentekovic, Darko
Format:	Journal Article
Language:	English
Published:	American Chemical Society 16-11-2012
Online Access:	Get full text
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Summary:	The original synthesis of glycopyrrolate (NVA237) was revised and shortened into an essentially one-pot process. Without isolating the intermediates, their purification became obsolete, thereby increasing the possibility of the carry over of impurities. For that reason, the actual, potential, and theoretical impurities of the starting materials cyclopentyl mandelic acid and 1-methyl-pyrrolidin-3-ol as well as byproducts which may occur during the synthesis were thoroughly investigated; furthermore, their transformation to possible impurities in the drug substance along the new synthetic route was performed to exclude them as actual impurities in the drug substance with certainty. The question is raised how detailed such investigationwhich are fairly manageable for a simple product like glycopyrrolateneed to be.
ISSN:	1083-6160 1520-586X
DOI:	10.1021/op3001788