title: Optimization of a novel headspace-solid-phase microextraction-gas chromatographic method by means of a Doehlert uniform shell design for the analysis of trace level ethylene oxide residuals in sterilized medical devices.
abstract: Medical devices sterilized by ethylene oxide (EtO) retain trace quantities of EtO residuals, which may irritate patients' tissue. Reliably quantifying trace level EtO residuals in small medical devices requires an extremely sensitive analytical method. In this research, a Doehlert uniform shell design was utilized in obtaining a response surface to optimize a novel headspace-solid-phase microextraction-gas chromatographic (HS-SPME-GC) method developed for analyzing trace levels of EtO residuals in sterilized medical devices, by evaluating sterilized, polymer-coated, drug-eluting cardiovascular stents. The effects of four independent experimental variables (HS-SPME desorption time, extraction temperature, GC inlet temperature and extraction time) on GC peak area response of EtO were investigated simultaneously and the most influential experimental variables determined were extraction temperature and GC inlet temperature, with the fitted model showing no evidence of lack-of-fit. The optimized HS-SPME-GC method demonstrated overall good linearity/linear range, accuracy, repeatability, reproducibility, absolute recovery and high sensitivity. This novel method was successfully applied to analysis of trace levels of EtO residuals in sterilized/aerated cardiovascular stents of various lengths and internal diameter, where, upon heating, trace EtO residuals fully volatilized into HS for extraction, thereby nullifying matrix effects. As an alternative, this novel HS-SPME-GC method can offer higher sensitivity compared with conventional headspace analyzer-based sampling.
authors.affiliation: Sterile Process Technology (SPT), a Division of the Johnson and Johnson Corp., 930 US Route 202 South, Raritan, NJ 08869, USA. MDiCicc1@its.jnj.com
authors.forename: Michael P
authors.initials: MP
authors.lastname: DiCicco
authors.forename: Bridget
authors.initials: B
authors.lastname: Lang
authors.forename: Thomas I
authors.initials: TI
authors.lastname: Harper
mesh_terms: D002849:Chromatography, Gas / Q000379:methods*; D004202:Disinfectants / Q000032:analysis*; D054855:Drug-Eluting Stents; D005027:Ethylene Oxide / Q000031:analogs & derivatives / Q000032:analysis*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D052617:Solid Phase Microextraction / Q000379:methods*; D013242:Sterilization; D013696:Temperature
chemical_list: D004202:Disinfectants; D005027:Ethylene Oxide