title: Purity profile of the indoloquinone anticancer agent EO-9 and chemical stability of EO-9 freeze dried with 2-hydroxypropyl-beta-cyclodextrin.
abstract: Two new bladder instillations of the investigational anticancer agent EO-9 containing 2-hydroxypropyl-beta-cyclodextrin (HP beta CD) and the alkalizers sodium bicarbonate (NaHCO3) and tri(hydroxymethyl)aminomethane (Tris) were developed. During the stability study of these freeze-dried products, formation of new degradation products was seen. We have characterized these products by high performance liquid chromatography in combination with photodiode array detection and mass spectrometry. In total, five new degradation products were identified of which three were detected in both freeze-dried products and two only in the freeze-dried product composed of EO-9/HP beta CD/NaHCO3. Furthermore, the purity profile of two lots of EO-9 drug substance was investigated. Five, probably synthetic intermediates were found. However, the amount of total impurities was very small for both lots of drug substance and below acceptable international limits for pharmaceutical use.
authors.affiliation: Department of Pharmacy & Pharmacology, Slotervaart Hospital/The Netherlands Cancer Institute, Louwesweg 6, 1066 EC Amsterdam, The Netherlands.
authors.forename: S C
authors.initials: SC
authors.lastname: van der Schoot
authors.forename: L D
authors.initials: LD
authors.lastname: Vainchtein
authors.forename: B
authors.initials: B
authors.lastname: Nuijen
authors.forename: A
authors.initials: A
authors.lastname: Gore
authors.forename: D
authors.initials: D
authors.lastname: Mirejovsky
authors.forename: L
authors.initials: L
authors.lastname: Lenaz
authors.forename: J H
authors.initials: JH
authors.lastname: Beijnen
mesh_terms: D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000970:Antineoplastic Agents / Q000032:analysis*; D001388:Aziridines / Q000032:analysis*; D002851:Chromatography, High Pressure Liquid; D004355:Drug Stability; D005079:Excipients; D005612:Freeze Drying; D006863:Hydrogen-Ion Concentration; D045563:Indolequinones / Q000032:analysis*; D013058:Mass Spectrometry; D013056:Spectrophotometry, Ultraviolet; D047392:beta-Cyclodextrins
chemical_list: D000970:Antineoplastic Agents; D001388:Aziridines; D005079:Excipients; D045563:Indolequinones; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; C060817:apaziquone