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Analytical and Bioanalytical Chemistry

, Volume 411, Issue 11, pp 2425–2437 | Cite as

Assessment of CE-based baseline disturbances using simulation and targeted experimental evaluation—impact on the purity determination of therapeutic proteins

  • Yan GuEmail author
  • Sergey Voronov
  • Julia Ding
  • Nesredin Mussa
  • Zheng Jian Li
Research Paper
  • 55 Downloads

Abstract

The baseline instability for capillary electrophoretic analysis is an intrinsic feature of the technique, which has not been thoroughly examined for its impact on therapeutic protein purity analysis with the capillary electrophoresis-sodium dodecyl sulfate (CE-SDS) applications. For the particular CE-SDS application, this phenomenon was manifested through peak migration time shifts and sliding of the superimposed baseline profile. These dual phenomena are closely associated so that experimental assessment alone may not shed enough light to the underlying drivers. In the current study, both experimental and simulation approaches were employed to assess the systematic drifts. Computer simulation was used to decipher the two underlying factors and test their contributions toward purity and impurity peak determination inaccuracies. The data generated in this study demonstrated that the electrophoretic baseline disturbance had more pronounced impact on the purity data than the migration time shift. In addition, the potential contributing factors to the baseline disturbances were assessed experimentally which indicated that the source is related to thermal disruption during a sample run and the unique baseline patterns came from the background electrolytes. To improve data reproducibility for drug purity testing in the industrial setting and quality control (QC) environment, it is recommended to run shorter injection sequences including fewer samples and closely monitor the baseline drift for accurate integration. Those methods would help reduce the impact of systematic drift and disturbances.

Graphical abstract

Keywords

CE-SDS Systematic variation Computer simulation Baseline disturbance Migration time shift 

Abbreviations

CE

Capillary electrophoresis

CFR

Code of Federal Regulations

CGE

Capillary gel electrophoresis

DTT

Dithiothreitol

IgG

Immunoglobin G

FDS

Finite difference scheme

GMP

Good manufacturing practice

HHL

Heavy-heavy-light, intact IgG molecule missing one light chain

HH

Heavy-heavy, intact IgG molecule missing both light chains

QC

Quality control

SDS

Sodium dodecyl sulfate

TCEP

Tris(2-carboxyethyl)phosphine

Notes

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

216_2019_1704_MOESM1_ESM.pdf (496 kb)
ESM 1 (PDF 495 kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Yan Gu
    • 1
    Email author
  • Sergey Voronov
    • 1
  • Julia Ding
    • 1
  • Nesredin Mussa
    • 1
    • 2
  • Zheng Jian Li
    • 1
  1. 1.Biological Process and Product DevelopmentBristol-Myers Squibb CompanyDevensUSA
  2. 2.Ultragenyx Pharmaceutical Inc.NovatoUSA

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