An Overview on Chemical Derivatization and Stability Aspects of Selected Avermectin Derivatives

Abstract

Naturally occurring avermectins (AVMs) and its derivatives are potent endectocide compounds, wellknown for their novel mode of action against a broad range of nematode and anthropod animal parasites. In this review, chemical and pharmaceutical aspects of AVM derivatives are described including stability, synthetic and purification processes, impurities and degradation pathways, and subsequent suggestions are made to improve the chemical stability. It has been found out that unique structure of AVM molecules and presence of labile groups facilitated the derivatization of AVM into various compounds showing strong anthelmintic activity. However, the same unique structure is also responsible for labile nature related to sensitive stability profile of molecules. AVMs are found to be unstable in acidic and alkaline conditions. In addition, these compounds are sensitive to strong light, and subsequently presence of photo-isomer in animals treated topically with AVM product is well known. The pharmacoepial recommendations for addition of antioxidant into drug substance, as well as its products, arises from the fact that AVM are very sensitive to oxidation. Formations of solvates, salts, epoxides, reduction of double bonds and developing liquid formulation around pH 6.2, were some chemical approaches used to retard the degradation in AVM. This coherent review will contribute towards the better understanding of the correlation of chemical processes, stability profile and biological activity; therefore, it will help to design the shelf-life stable formulations containing AVMs.

The development of an efficient mass balance approach for the purity assignment of organic calibration standards

“…Optimised chromatographic conditions successfully separated the expected impurities [29] from the main analyte (Fig. 5) as well as a tentatively assigned diastereomer of avermectin B 1a (rt=26.9 min) which we believe to be the first time this has been reported.…”

“…S3) confirmed further bias in the TGA result with both dichloromethane and diethyl ether being present in 9 and 7 mg/g mass fraction, respectively. This example serves, once again, to demonstrate the importance of using 1 H NMR spectroscopy to cross-check the results of more traditional [29] c Distinct shoulders are observed on either side of the λ max techniques used in purity determination. Conscious of the fact that solvent content will not always be so readily identified, we have introduced a qualitative headspace GC-MS analysis to our suite of characterisation techniques.…”

Получение Авермектинов: Биотехнологии И Органический Синтез

“…Технологии получения авермектинов традиционно (2) предполагают получение высокопродуктивных штаммов, синтезирующих предпочтительно авермектины В1, оптимизацию питательных сред для культивирования продуцента и производство полусинтетических аналогов авермектинов В1 с улучшенными физико-химическими и фармакологическими свойствами (28)(29)(30). В последние годы развивается еще одно направление -синтез желаемых продуктов (например, ивермектина, мильбемицинов) методами синтетической биологии (31)(32)(33)(34).…”

Evaluation of degradation kinetics for abamectin in formulations using a stability indicating method

“…There are also reports describing oxidation of the oxahydrindene unit as well as photodegradation, resulting in the 8,9-Z isomer of ABM molecule (13)(14)(15). These degradation products (DPs) such as monosaccharide, aglycone, 2-epi-, and D2,3-, etc., are known to lack the necessary anthelmintic actions of AVM (16).…”