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purity_quest

Boosting purification of liraglutide with the GLP-1 agonist purification toolbox

An example on how the Kromasil® GLP-1 agonist purification toolbox can be used to boost the purification of liraglutide, a common GLP-1 receptor agonist in pharmaceutical applications.

Working from a low purity peptide synthesis crude can be a challenge easily demanding 3 or 4 purification steps to reach proper product purity. The proposed process from the Kromasil GLP-1 agonist purification toolbox is taking a 50% purity peptide crude to a final purity of 99.6% in a 2-step process using the same stationary phase, a Kromasil 10 µm C4, all along.

The purification heavy lifting is performed in the first step with an ammonium acetate buffer in the mobile phase. The anti-Langmurian overload profile is efficient at pushing away tail impurities (illustrated with red in the figure), but quite some front-end impurities are removed as well. In that single step brings purity in the recovered fraction pool (in light blue in the figure) up to 95% (from the initial 50%) at a 90% product yield. With a load of 40 g liraglutide / kg Kromasil C4 , the productivity of the step is 5.7 g liraglutide /(kg Kromasil C4 · h).

prep chromatogram of purification first step
First purification step: prep chromatogram. Analysis of pooled fractions. Light blue area: collected fractions of target product. Light red area: target impurities to be removed by this step.

In the second step from the toolbox using ammonium carbonate buffer, the Langmurian overloading profile aims at the removal of the remaining front impurities in the pooled fractions from the first purification step, achieving the final liraglutide purity of over 99.5% in the recovered fractions. With a product recovery yield of 78% and a productivity of 7.1 g liraglutide /(kg Kromasil C4 · h) over that step, the total yield over the purification process was 66.5%.

prep chromatogram of purification second step
Second purification step: prep chromatogram. Analysis of pooled fractions. Light blue area: collected fractions of target product. Light red area: target impurities to be removed by this step.

With the newly developed Kromasil GLP-1 agonist purification toolbox it is possible to develop excellent purification methods which gives high purity and yields, boosting the productivity of GLP-1 agonist manufactures.