Methods for the analysis of galanthamine and its extraction from laboratory to industrial scale

Abstract

Galanthamine is a competitive acetylcholinesterase (AChE) inhibitor naturally produced by the plants of Amaryllidaceae family. It is used as a treatment against Alzheimer's disease (AD) and is an FDA approved drug. The content of this metabolite varies between different plant species as well as within the same species. To measure the galanthamine levels diverse extraction and pre-analytical methods at laboratory scale have been developed for chromatographic and spectroscopic analysis. Galanthamine identification and quantification methods are changing over time due to improvements in equipment. Development of new technologies also leads to new methods. At lab scale, there are various methods which can be used for the extraction of galanthamine from different sources. The final identification and quantitation of the alkaloid(s) can be achieved with different methods such as thin layer chromatography (TLC), liquid chromatography (HPLC, UPLC, LC-MS), GC(-MS) and nuclear magnetic resonance (NMR) spectroscopy. All these methods have been reviewed in this chapter. From different studies, it is evident that extraction time and method robustness are the basic parameters for selecting the best method. TLC, HPLC and GC-FID can be used for quick identification and quantitation, but for proper analysis standard reference compounds are required. Moreover, pre-analytical sample preparation is time consuming for LC-MS and particularly GC–MS. Considering these aspects 1HNMR spectroscopy is the fastest and best reproducible method, because compounds are identified and quantified based on their highly specific signals in the spectra of the extracts. For large scale extraction various methods (solvent extraction, microwave-assisted extraction, and supercritical carbon dioxide extraction) have been developed for galanthamine extraction and purification. But mostly classical organic solvent extraction is used in industrial production due to low cost and availability of large-scale extraction facilities. Galanthamine recovery rate is relatively low in this method. Recently, progress have been made towards developing better methods. Among these developments, super critical fluid (carbon dioxide) extraction has great interest because it is a more environmentally friendly (green) technology. Although the solvent extraction methods are commercially applied to date, there is still a possibility for improvement in the extraction and purification process of galanthamine from plants as based on the present yields, still only about 50% of galanthamine present is obtained from the plant material in the large-scale extraction process.