Reference Standard Certification

What are Reference Standards?

A Reference standard is defined as a highly characterized material suitable to test the identity, strength, quality and purity of substances for pharmaceutical use and medicinal products.

At J-Star Research, the preparation of high-quality reference standards in appropriate quantities begins when we start to make demo batches or toxicology batches for new drug candidates. Extra purification may be applied in the preparation of a reference standard. This material is then characterized via a suite of analytical and NMR techniques. A characterization report is written based on the filing requirements (upon request from the client).

J-Star Research scientists divide reference standards into two groups: Retention Markers and Quantitative Reference Standard.

Retention Markers

These are typically starting materials, impurities, intermediates, and drug substances used qualitatively in test methods to mark retention times and identify peaks, as components of mixtures to establish resolution, or to establish identity via spectral comparison. They are not used for quantitative weight % assays.

Quantitative Reference Standards

These reference standards are typically starting materials, intermediates, or drug substances used in test methods as working standards for quantitative weight % assay determinations of major components.

  • Quantitative reference standards can also be starting materials, intermediates, or other impurities used in test methods as working standards for weight % impurity determinations.
  • Quantitative reference standards can also serve as retention markers and similar qualitative reference standards.

Characterization of Reference Standards

The following tests are typically used to characterize reference standards intended for use in qualitative tests. This list may be altered as judged appropriate for a given project or as requested by a client:

  • Physical appearance
  • Two identification tests, typically including NMR, IR, or Mass spectrum
  • Specific rotation (for chiral compounds)

The following tests are typically used to characterize reference standards intended for use in quantitative weight % assays for both, major components and impurities. This list may be altered as judged appropriate for a given project or as requested by a client:

  • Physical appearance
  • Two identification tests, typically including NMR, IR, or Mass spectrum
  • Specific rotation (for chiral compounds)
  • Area % purity by HPLC or GC, with impurity profile
  • Residual solvents by GC or Loss on Drying
  • Water content by Karl-Fischer titration or Loss on Drying
  • Melting point (for solids)
  • Inorganic impurities (residue on ignition / sulfated ash)
  • Solid form by X-ray diffraction (for solids)
  • Assigned purity or purity factor

In all cases, a Certificate of Analysis (COA) will be provided to the client.