CEI-MS-12 — Residual solvent determination by static headspace gas chromatography
Residual solvent determination by static headspace gas chromatography
§1Scope
§1.1Scope
Applies to synthetic peptides and small molecules where solvents of ICH class 1 or 2 were used in synthesis or purification. The Institute records that this determination is absent from the research-supply channel entirely.
§2Principle
The sample is equilibrated in a sealed vial at elevated temperature. Volatile solvents partition into the headspace according to their partition coefficients, and an aliquot of headspace is transferred to a gas chromatograph. Quantification is against standards prepared in the same matrix, because the partition coefficient depends on the matrix and an aqueous calibration cannot be applied to a lyophilised solid without a matrix-matched correction.[1,2]
§3Apparatus and reagents
§3.1Apparatus
- Gas chromatograph with a static headspace autosampler and a flame-ionisation detector
- Capillary column of a stationary phase suitable for the solvent set, typically a 6 % cyanopropylphenyl / 94 % dimethylpolysiloxane phase
- Headspace vials with crimped septum closures
- Thermostatted equilibration oven
§3.2Reagents and reference materials
- Reference solvents of stated purity for each analyte
- Dimethyl sulfoxide or water as diluent, matched to the sample matrix
- Nitrogen or helium carrier gas
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 Q3C(R9) Impurities: Guideline for Residual Solvents. ICH Harmonised Guideline 2024;Step 4 version. identifier not held by the Institute
- United States Pharmacopeial Convention. General Chapter ⟨1225⟩ Validation of Compendial Procedures. 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.