Preparative High Performance Liquid Chromatography (HPLC) Technology from Novasep

The most versatile chromatography technique

Preparative HPLC

HPLC is the most well-known analytical technique used in the fine chemical and pharmaceutical industries. The acronym “HPLC” stands for High Performance Liquid Chromatography, rather than “high pressure”. However, the performance (typically measured by the number of theoretical plates per meter) is obtained by using stationary phases with small particle size (typically 5 to 20 µm), which in turn, generates a high pressure drop and a high operating pressure.

Although preparative HPLC is very similar to analytical HPLC, instead of injecting a small amount of product to maximize the resolution, the amount of feed is very high in order to maximize the purification productivity and minimize the amount of solvent used.

For chromatographic separations performed using isocratic eluents, productivity can be further increased and eluent consumption reduced by “stacking” the injections, as explained below. Using a standard injection process (Figure 7a), a new injection is performed once the last compound exits the column. The idea of “stacking” injections is to inject after a time corresponding to the chromatographic cycle time, meaning that the feed injections occur in a “non empty column” as the previous injection is still inside the column, as shown in the figure below. This very simple approach allows the eluent consumption to be reduced by more than half.

(a) Standard Injections

(b) Stacked Injections

In addition to being easy to use and implement, preparative HPLC does not require ancillary equipment at small scale and the eluent can easily be recycled at large-scale. It is also a highly versatile technique as it theoretically works for all types of compounds (polar, apolar, protic, highly toxic molecules, etc.). Thus it is an “all-purpose” technique that can be used for early and late development phases as well as commercial production, in particular to purify a single component from a complex mixture.

Click here to discover our High Performance Liquid Chromatography systems: Prochrom® Hipersep.

Click here to discover our High Performance Liquid Chromatography systems for biopharmaceutical manufacturing: Prochrom® Hipersep-Bio.

Solvent recycling for green separations

Solvent recycling is a key aspect in preparative chromatography which can be designed as a unit operation that includes solvent recycling with the dry feed mixture being injected while dry separated compounds are recovered. Well-designed preparative HPLC plants typically recycle more than 95% of solvents, and up to 99+%.

Different techniques can be applied depending on the elution condition: isocratic (i.e. with a constant mobile phase composition) or gradient conditions.

During a separation, the solvent is recovered from evaporators and dryers while pure dry compounds are recovered. The recycled solvent is reused to elute the column and to dissolve the dry feed mixture. Only a small amount of fresh solvent is automatically added to the recycled one in order to adjust the eluent composition, using a patented technology.

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