Method development and validation for the determination of 2,4,6-tribromoanisole, 2,4,6-tribromophenol, 2,4,6-trichloroanisole, and 2,4,6-trichlorophenol in various drug products using stir bar sorptive extraction and gas chromatography–tandem mass spectr

Recently, haloanisoles and halophenols are associated with multiple product recall situations in the pharmaceutical industry. The majority of the recalls are associated with consumer complaints due to the presence of 2,4,6-tribromoanisole, as extremely low levels of this component can be easily detected by the human nose. As part of the root cause analysis to address the cause of the consumer complaints, a GC–MS/MS based analytical method combined with stir bar sorptive extraction (SBSE) sample preparation was developed for determination of halophenols and haloanisoles from various drug product formulations. The method also applies to the analysis of 2,4,6-tribromoanisole analysis in various packaging materials. The optimized MS/MS method is based on component-specific MRM transitions. The detection limit is component dependent and in the range of 1–100 pg/tablet for solid dosage formulations and 0.04–4 ng/L for water based solutions. Deuterated tribromoanisole was used as internal standard for quantitation. The paper also may provide guidance for performing trace level method validation in the regulated Pharmaceutical Industry.

► Trace level method validation practice presented for taint components.
► TBA, TCA, TBP, TCP were analyzed in solid dosage formulations.
► Method based stir bar sorptive extraction combined with GC–MS/MS.
► Trace level method validation complies with 2002/657 EU Council Directive.