Structural identification of extractables from rubber closures used for pre-filled semisolid drug applicator by chromatography, mass spectrometry, and organic synthesis.
Extractables or leachables from rubber closures used for drug products can potentially be detrimental since some of these rubber extractables are known to be toxic and pyrogenic. In addition, these extractables could interfere with analysis or even affect the stability profile of the active ingredients. For these reasons, it became necessary to identify structures of the possible extractables or leachables from rubber closures so that their potential impact on the drug products that are in direct contact with rubber closures could be evaluated. In this report, five species, 4-(1,1-dimethyl-propyl)-phenol (1), sulfur (2), 2,6-di-tert-butyl-[1,4] benzoquinone (3), furan-2-yl-(5-hydroxymethyl-furan-2-yl)-methanol (4), and 2-bromo-4-(1,1-dimethyl-propyl)-phenol (5), were found to be possible extractables from the rubber closures which were used in a selected pre-filled semisolid drug applicator. A strategy combining HPLC, GC, mass spectrometry, and organic synthesis was utilized.
Zhang
Fa
F
Johnson & Johnson C&PPW, Analytical R&D, Skillman, NJ 08558, USA. fzhang1@cpcus.jnj.com
Chang
Alan
A
Karaisz
Ken
K
Feng
Rong
R
Cai
Jane
J
D016227:Benzoquinones / Q000302:isolation & purification; D004340:Drug Contamination / Q000517:prevention & control*; D004349:Drug Packaging / Q000592:standards; D005663:Furans / Q000302:isolation & purification; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods; D019800:Phenol / Q000302:isolation & purification; D012408:Rubber / Q000032:analysis* / Q000737:chemistry; D013455:Sulfur / Q000302:isolation & purification
D016227:Benzoquinones; D005663:Furans; D019800:Phenol; D013455:Sulfur; D012408:Rubber; C051290:2-tert-butyl-4-quinone; C039281:furan