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Alternative solvents can make preparative liquid chromatography greener



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Green Chem., 2015, Advance Article
DOI: 10.1039/C5GC00887E, Paper
Yao Shen, Bo Chen, Teris A. van Beek

Alternative solvents can make preparative liquid chromatography greener

Yao Shen,*ab   Bo Chenb and   Teris A. van Beeka  
*Corresponding authors
aLaboratory of Organic Chemistry, Wageningen University, Dreijenplein 8, 6703 HB Wageningen, The Netherlands
bKey Laboratory of Phytochemical R&D of Hunan Province, Hunan Normal University, Changsha, PR China
Greener ethanol, acetone and ethyl acetate provided better chromatographic resolution in preparative RP-HPLC than the traditional methanol, acetonitrile and tetrahydrofuran.

Alternative solvents can make preparative liquid chromatography greener

To make preparative Reversed-Phase High Performance Liquid Chromatography (RP-pHPLC) greener, alternative solvents were considered among others in terms of toxicity, cost, safety, workability, chromatographic selectivity and elution strength. The less toxic solvents ethanol, acetone and ethyl acetate were proposed as possible greener replacements for methanol, acetonitrile and tetrahydrofuran (THF).

For testing their feasibility, five ginkgo terpene trilactones were used as model analytes. The best “traditional” eluent, i.e., methanol–THF–water (2 : 1 : 7) was used as the benchmark. A generic two-step chromatographic optimization procedure by UHPLC consisting of (1) a simplex design using the Snyder solvent triangle and (2) HPLC modelling software was used.

In the first step, two ternary mixtures were found (acetone–ethyl acetate–water (20.25 : 3.75 : 76) and ethanol–ethyl acetate–water (9.5 : 7.5 : 83)), which already gave better results than the benchmark. The second step in which the influence of the gradient time, temperature and ratio of the two best ternary isocratic solvents was studied, led to an optimal 10.5 min gradient and a minimum resolution of 5.76.

In the final step, scale-up from 2.1 to 22 mm i.d. pHPLC columns proceeded successfully. When 0.5 g of the sample was injected, baseline separation was maintained. Chromatographic and absolute purities for products exceeded 99.5% and 95% respectively. This example shows that using less toxic and cheaper solvents for pHPLC can go hand in hand with higher productivity and less waste.


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