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Issue 7, 2015
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Alternative solvents can make preparative liquid chromatography greener

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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.

Graphical abstract: Alternative solvents can make preparative liquid chromatography greener

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Article information

27 Apr 2015
02 Jun 2015
First published
02 Jun 2015

Green Chem., 2015,17, 4073-4081
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Author version available

Alternative solvents can make preparative liquid chromatography greener

Y. Shen, B. Chen and T. A. van Beek, Green Chem., 2015, 17, 4073
DOI: 10.1039/C5GC00887E

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