CEI-MS-21 — Freeze–thaw and in-use stability assessment of reconstituted peptide solutions
Freeze–thaw and in-use stability assessment of reconstituted peptide solutions
§1Scope
§1.1Scope
Applies to the assessment of any in-use period claimed for a reconstituted peptide solution, and to the practice of freezing reconstituted solutions for later use. The Institute publishes no in-use claim for reconstituted research material and this standard states what would be required to support one.
§2Principle
Freezing a peptide solution concentrates solutes in the shrinking liquid fraction, raising local ionic strength and driving pH shifts as buffer components crystallise differentially. Phosphate buffers are particularly prone to a large pH drop on freezing. Ice–liquid interfaces denature and aggregate proteins and amphipathic peptides. These effects are not detected by a reverse-phase purity determination and require an aggregate determination alongside.[1,2]
§3Apparatus and reagents
§3.1Apparatus
- Controlled-rate freezer or validated −20 °C and −80 °C storage
- Refrigerated storage at 2–8 °C with continuous monitoring
- pH meter suitable for small volumes
- HPLC and size-exclusion systems as CEI-MS-01 and CEI-MS-11
§3.2Reagents and reference materials
- Diluent as used in practice, including bacteriostatic water where that is the practice being assessed
- Reference standard
References cited on this page
References are numbered in order of first citation in this document. Each superscript in the text links to its entry below.
- International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use. ICH Q1A(R2) Stability Testing of New Drug Substances and Products. ICH Harmonised Tripartite Guideline 2003;Step 4 version. identifier not held by the Institute
- Manning MC, Chou DK, Murphy BM, Payne RW, Katayama DS. Stability of protein pharmaceuticals: an update. Pharmaceutical Research 2010;27(4):544–575. doi:10.1007/s11095-009-0045-6 · PMID 20143256
Identifiers are reproduced only where the Institute holds them. Where a digital object identifier or PubMed identifier is not shown, the Institute has recorded the journal and year and has not constructed an identifier.