1: Pharm Res. 2006 Sep;23(9):2141-8. Epub 2006 Aug 9.

Chemical analysis of solid-state irradiated human insulin.

Terryn H, Vanhelleputte JP, Maquille A, Tilquin B.

Laboratory of Chemical and Physicochemical Analysis of Drugs (CHAM), Universite
Catholique de Louvain, CHAM 72.30, Avenue E. Mounier, 72, B- 1200, Brussels,
Belgium. helene.terryn@cham.ucl.ac.be

PURPOSE: To study the chemical modifications induced upon irradiation of solid
human insulin at radiosterilization doses and investigate the influence of the
absorbed dose on radiolysis. MATERIALS AND METHODS: Volatile radiolytic products
were monitored by gas chromatography coupled with mass spectrometry (GC-MS) and
non-volatile products by two different high performance liquid chromatography
(HPLC) methods: the formation of higher molecular weight proteins was assessed
by size exclusion liquid chromatography whereas assays for related compounds and
chemical potency tests were carried out using reverse-phase HPLC-UV.
Conformational changes were investigated by measurements of circular dichroism.
RESULTS: After gamma irradiation at 10 kGy, the recovery of insulin was 96.8%;
higher molecular weight proteins accounted for 0.35% (relative peak area) and
other related compounds (including A21 desamido insulin) represented 1.29%. No
major structural changes and no volatile radiolytic compounds were detected.
CONCLUSION: Human insulin samples irradiated in the solid-state at 10 kGy (gamma
rays) and 14 kGy (electron-beam) meet the European Pharmacopoeia requirements
and can be considered as quite stable towards radiation from a chemical analysis
viewpoint.

PMID: 16952005 [PubMed - indexed for MEDLINE]

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