title: 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 spectrometry detection.
abstract: 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.
authors.affiliation: Analytical Research and Development, Process and Product Scientific Solutions, Johnson and Johnson, 1000 Route 202S, Raritan, NJ 08869, USA.
authors.forename: Jiun-Tang
authors.initials: JT
authors.lastname: Huang
authors.forename: Lori
authors.initials: L
authors.lastname: Alquier
authors.forename: Joyce P
authors.initials: JP
authors.lastname: Kaisa
authors.forename: Gail
authors.initials: G
authors.lastname: Reed
authors.forename: Timothy
authors.initials: T
authors.lastname: Gilmor
authors.forename: Gyorgy
authors.initials: G
authors.lastname: Vas
mesh_terms: D000840:Anisoles / Q000032:analysis* / Q000302:isolation & purification; D005591:Chemical Fractionation / Q000379:methods*; D002733:Chlorophenols / Q000032:analysis* / Q000302:isolation & purification; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods*; D057230:Limit of Detection; D016014:Linear Models; D010636:Phenols / Q000032:analysis* / Q000302:isolation & purification; D015203:Reproducibility of Results; D013607:Tablets / Q000737:chemistry; D053719:Tandem Mass Spectrometry / Q000379:methods
chemical_list: D000840:Anisoles; D002733:Chlorophenols; D010636:Phenols; D013607:Tablets; C024564:2,4,6-trichlorophenol; C004554:2,4,6-tribromophenol