Set-up of large laboratory-scale chromatographic separations of poly(ethylene glycol) derivatives of the growth hormone-releasing factor 1-29 analogue

J Chromatogr A. 2002 Jan 25;944(1-2):141-8. doi: 10.1016/s0021-9673(01)01367-x.

Abstract

In this paper we report the scale-up of the purification of poly(ethylene glycol) (PEG) derivatives of the growth hormone-releasing factor 1-29, from laboratory scale (100 mg of bulk starting material) to larger scale (3 g of bulk), through the use of a cation-exchange TSK-SP-5PW chromatographic column. A one-step purification process capable of purifying large amounts of mono-PEGylated GRF species from the crude reaction mixture was developed. A simple, straightforward stepwise gradient elution separation was developed at laboratory scale and then scaled up with a larger column packed with a chromatographic resin with the same chemistry which maintained the laboratory-scale separation profile. Active material recovery and material purity remained constant through the scale-up from the 13-microm stationary phase to the 25-microm larger column. Overall, the gram GRF equivalent/batch process scale showed to be quite reproducible, and could be considered as a good platform for scale up to production scale.

MeSH terms

  • Cation Exchange Resins
  • Chromatography, Ion Exchange / methods*
  • Growth Hormone-Releasing Hormone / chemistry
  • Growth Hormone-Releasing Hormone / isolation & purification*
  • Peptide Fragments / chemistry
  • Peptide Fragments / isolation & purification*
  • Polyethylene Glycols / chemistry*
  • Reproducibility of Results

Substances

  • Cation Exchange Resins
  • Peptide Fragments
  • Polyethylene Glycols
  • Growth Hormone-Releasing Hormone
  • somatotropin releasing hormone (1-29)