PT  - JOURNAL ARTICLE
AU  - James Pang
AU  - Tim Blanc
AU  - John Brown
AU  - Steven Labrenz
AU  - Annabelle Villalobos
AU  - Anneli Depaolis
AU  - Srinivas Gunturi
AU  - Steve Grossman
AU  - Peter Lisi
AU  - George A. Heavner
TI  - Recognition and Identification of UV-absorbing Leachables in EPREX<sup>®</sup> Pre-filled Syringes: An Unexpected Occurrence at a Formulation—Component Interface
DP  - 2007 Nov 01
TA  - PDA Journal of Pharmaceutical Science and Technology
PG  - 423--432
VI  - 61
IP  - 6
4099  - http://journal.pda.org/content/61/6/423.short
4100  - http://journal.pda.org/content/61/6/423.full
SO  - PDA J Pharm Sci Technol2007 Nov 01; 61
AB  - During the period of 1998 to 2002, there was an increase in the incidence of antibody-positive pure red cell aplasia (PRCA) in patients receiving subcutaneous administration of EPREX (epoetinum alfa). As part of the investigation of this event, the aqueous formulation containing polysorbate 80, introduced in 1998, facilitated the leaching of small-molecule, aromatic compounds from the uncoated rubber syringe stoppers. The leachables were identified using Liquid Chromatography-Mass Spectroscopy, Electrospray Ionisation-MS/MS, Dithiothreitol reduction, and Hydrogen/Deuterium exchange. The major leachable was identified as a dialkylphenol disulfide, and the majority of the remaining peaks were identified as structural variants containing different numbers of sulfur atoms in the sulfide bridge. In this report, we describe the strategies and experimental designs that were used to overcome the analytical challenges and that led to successful structural identification of the leachables in EPREX pre-filled syringes with uncoated syringe stoppers.