Ergot alkaloid control in biotechnological processes and pharmaceuticals (a mini review)

Abstract

The control of ergot alkaloids in biotechnological processes is important in the context of obtaining new strain producers and studying the mechanisms of the biosynthesis, accumulation and secretion of alkaloids and the manufacturing of alkaloids. In pharmaceuticals, it is important to analyze the purity of raw materials, especially those capable of racemization, quality control of dosage forms and bulk drugs, stability during storage, etc. This review describes the methods used for qualitative and quantitative chemical analysis of ergot alkaloids in tablets and pharmaceutic forms, liquid cultural media and mycelia from submerged cultures of ergot and other organisms producing ergoalkaloid, sclerotias of industrial Claviceps spp. parasitic strains. We reviewed analytical approaches for the determination of ergopeptines (including their dihydro- and bromine derivatives) and semisynthetic ergot-derived medicines such as cabergoline, necergoline and pergolide, including precursors for their synthesis. Over the last few decades, strategies and approaches for the analysis of ergoalkaloids for medical use have changed, but the general principles and objectives have remained the same as before. These changes are related to the development of new genetically improved strains producing ergoalkaloids and the development of technologies for the online control of biotechnological processes and pharmaceutical manufacturing (“process analytical technologies,” PAT). Overall, the industry is moving toward “smart manufacturing.” The development of approaches to production cost estimation and product quality management, manufacturing management, increasing profitability and reducing the negative impact on personnel and the environment are integral components of sustainable development. Analytical approaches for the analysis of ergot alkaloids in pharmaceutical raw materials should have high enough specificity for the separation of dihydro derivatives, enantiomers and R-S epimers of alkaloids, but low values of the quantitative detection limit are less frequently needed. In terms of methodology, detection methods based on mass spectrometry have become more developed and widespread, but NMR analysis remains in demand because of its high accuracy and specificity. Both rapid methods and liquid chromatography remain in demand in routine practice, with rapid analysis evolving toward higher accuracy owing to improved analytical performance and new equipment. New composite electrochemical sensors (including disposable sensors) have demonstrated potential for real-time process control.