CEI-MS-05 — worked example

§6Worked example

§6.1Worked example — the limit for a milligram-scale peptide

1. A peptide is supplied in a 5 mg vial and the maximum contemplated administration is 1 mg in any one hour to a 70 kg subject.
2. Endotoxin limit = 5.0 EU/kg/h × 70 kg = 350 EU per hour.
3. Limit expressed per milligram of peptide = 350 EU ÷ 1 mg = 350 EU/mg.
4. A determination returning 4.2 EU/mg passes comfortably.
5. Now consider the same peptide where the contemplated administration is 20 mg in an hour, as would apply to a compound dosed at clinical scale. Limit = 350 ÷ 20 = 17.5 EU/mg, and the same 4.2 EU/mg result still passes.
6. The instructive case is a preparation returning 90 EU/mg. It passes for the 1 mg dose and fails for the 20 mg dose from an identical vial. An endotoxin figure without a stated dose is therefore not a pass or a fail; it is a number awaiting a question. This is why the Institute requires the intended dose to be stated alongside any endotoxin result.

§6.2Illustrative mass balance

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

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.