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Compound Evidence InstituteEvidence synthesis · established 2023Graded assessments of compounds, trials, methods and supply
Document set current to 30 July 2026
Methodological standard · Microbiological quality

CEI-MS-05 — Bacterial endotoxin determination in peptide preparations intended for parenteral use

Bacterial endotoxin determination in peptide preparations intended for parenteral use

Document identifier
CEI-MS-05
Series
Methodological standard
Version
1.1
Published
10 Sep 2025
Last reviewed
10 May 2026
Next review
10 May 2029
Identifier
10.71829/cei.meth.5
Certainty
High
Cycle
2025 Q3
Category
Microbiological quality

§1Scope

§1.1Scope

Applies to any peptide preparation that will be reconstituted and administered parenterally, including all material supplied for research use that is presented in a vial with a rubber closure. The Institute records that this determination is essentially absent from the research-supply channel.

§2Principle

Lipopolysaccharide from Gram-negative bacterial cell walls activates a coagulation cascade in Limulus amoebocyte lysate. The reaction is quantified either kinetically by turbidity, kinetically by chromogenic substrate cleavage, or by gel-clot endpoint. Results are expressed in endotoxin units per milligram of peptide, and are compared against a limit derived from the intended maximum dose.[1,2]

§3Apparatus and reagents

§3.1Apparatus

  • Microplate reader with 37 °C incubation and kinetic acquisition at 340 nm (turbidimetric) or 405 nm (chromogenic)
  • Depyrogenated glassware, or certified pyrogen-free disposables
  • Calibrated pipettes with pyrogen-free tips
  • Vortex mixer

§3.2Reagents and reference materials

  • Limulus amoebocyte lysate reagent with a stated labelled sensitivity
  • Control standard endotoxin traceable to the reference standard endotoxin
  • Lysate reagent water
  • Buffer for pH adjustment where the sample falls outside pH 6.0–8.0

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.

  1. United States Pharmacopeial Convention. General Chapter ⟨85⟩ Bacterial Endotoxins Test. United States Pharmacopeia — National Formulary (USP–NF) 2024;USP 2024 Issue 1. identifier not held by the Institute
  2. United States Pharmacopeial Convention. General Chapter ⟨71⟩ Sterility Tests. United States Pharmacopeia — National Formulary (USP–NF) 2024;USP 2024 Issue 1. identifier not held by the Institute

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