Article ID Journal Published Year Pages File Type
2480548 European Journal of Pharmaceutical Sciences 2014 11 Pages PDF
Abstract

HPLC analysis of drug products containing bisoprolol fumarate and lactose revealed the presence of N-formylbisoprolol, which is a final product of the Maillard reaction. Formulations containing secondary amines and reducing carbohydrates are prone to the condensation of amine and carbonyl functional groups and formation of glycosylamines in pharmaceutically relevant conditions. Further rearrangement occurs in the presence of a nucleophile and leads to the formation of 1-deoxy-1-amino-2-ketose also known as the Amadori Rearrangement Product (ARP). The influence of water content, carbohydrate, and lubricant types on the reaction rate was tested. The reaction progress was monitored by HPLC and UV–Vis spectrophotometry. The structures of intermediates were confirmed by the LC/MS2 analysis. N-formylbisoprolol – the final reaction product – was synthesised and characterised by LC/MS2, H1 and C13 NMR.

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Related Topics
Health Sciences Pharmacology, Toxicology and Pharmaceutical Science Drug Discovery
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