title: Determination of residual isobutylene oxide--a genotoxic starting material in a drug substance by static headspace gas chromatography.
abstract: A sensitive static headspace gas chromatography (sHS-GC) method is developed and validated for the determination of residual isobutylene oxide (IBO)-a genotoxic starting material in a drug substance for Phase I clinical trial studies. The experimental parameters, such as headspace vial pressure, headspace oven temperature, vial equilibration time, column flow rate, and GC oven temperature programs are optimized. Under the optimal conditions, the recovery is between 89.3% and 102.4% for spiked samples at three levels of IBO concentration in triplicates in sample preparations. Limits of quantitation (LOQ) and detection (LOD) of the standard solutions are 0.048 and 0.018 microg/mL, respectively. Linear range from 0.018 to 6 microg/mL is obtained with a correlation coefficient of 0.9999. The method is applied to determine residual IBO in drug substance samples from different batches.
authors: Analytical Research & Development, Amgen Inc., Thousand Oaks, CA 91320, USA.
authors: Jun
authors: J
authors: Han
authors: David
authors: D
authors: Yeung
authors: Fang
authors: F
authors: Wang
authors: David
authors: D
authors: Semin
mesh_terms: D002849:Chromatography, Gas / Q000379:methods*; D004852:Epoxy Compounds / Q000032:analysis*; D009153:Mutagens / Q000032:analysis*; D004364:Pharmaceutical Preparations / Q000737:chemistry; D012680:Sensitivity and Specificity; D012995:Solubility; D035501:Uncertainty
chemical_list: D004852:Epoxy Compounds; D009153:Mutagens; D004364:Pharmaceutical Preparations; C531329:isobutylene oxide