Carry Over of Impurities: A Detailed Exemplification for Glycopyrrolate (NVA237)
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- 作者：Thomas Allmendinger ; Dominique Bixel ; Adrian Clarke ; Laura Di Geronimo ; Jean-Wilfried Fredy ; Marco Manz ; Elena Gavioli ; Regine Wicky ; Martin Schneider ; Fabien J. Stauffert ; Markus Tibi ; Darko Valentekovic
- 刊名：Organic Process Research & Development
- 出版年：2012
- 出版时间：November 16, 2012
- 年：2012
- 卷：16
- 期：11
- 页码：1754-1769
- 全文大小：797K
- 年卷期：v.16,no.11(November 16, 2012)
- ISSN：1520-586X
文摘
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鈥攚hich are fairly manageable for a simple product like glycopyrrolate鈥攏eed to be.