title: Fast and fully automated analytical method for the screening of residues of aziridine and 2-chloroethylamine in pharmaceutical active principles.
abstract: A simple, fast and fully automated method for the screening of aziridine (AZD) and 2-chloroethylamine (CEA) in active pharmaceutical ingredients (API) has been developed. The method is based on the in-fiber derivatization of the amines extracted from the sample headspace (previously dissolved or suspended in alkaline water) with 2,3,4,5,6-pentafluorobenzoyl chloride (PFBCl) previously adsorbed in the PDMS/DVB solid phase microextraction (SPME) fiber. The derivatives formed are further desorbed and analyzed in a gas chromatograph with negative ion chemical ionization mass spectrometry (GC-NCI-MS) using methane as reagent gas. The different operational parameters of the procedure have been optimized to get highest sensitivity. The validation of the method, however, revealed a poor repeatability, particularly evident in water-soluble APIs (RSD>20% for AZD). In spite of that, the low detection limits (1-3ngg(-1) for AZD and CEA), speed (44min total analysis time) and automation make that this method can be satisfactorily used as screening tool to accept or reject API batches attending to their volatile amine content and a critical specified value derived from the 1.5μg/day Threshold of Toxicological Concern (TTC) and maxima daily dosages. This was shown by analyzing seventy-five fluvoxamine maleate samples containing known levels of AZD and CEA (between 0.05 and 1.05μgg(-1)) in intermediate reproducibility conditions to get reliable estimations of precision and linearity. From these data, acceptance, rejection and non-conclusive areas of response are defined for both analytes at different confidence and replication levels using normal statistics. The method was satisfactorily applied to real fluvoxamine maleate samples.
authors.affiliation: Laboratory for Flavor Analysis and Enology, Institute of Engineering of Aragón, I3A, Department of Analytical Chemistry, Faculty of Sciences, University of Zaragoza, 50009 Zaragoza, Spain.
authors.forename: Julián
authors.initials: J
authors.lastname: Zapata
authors.forename: Jorge
authors.initials: J
authors.lastname: Temprado
authors.forename: Laura
authors.initials: L
authors.lastname: Mateo-Vivaracho
authors.forename: Vicente
authors.initials: V
authors.lastname: Ferreira
mesh_terms: D000327:Adsorption; D001331:Automation; D001388:Aziridines / Q000032:analysis*; D005021:Ethylamines / Q000032:analysis*; D008401:Gas Chromatography-Mass Spectrometry / Q000295:instrumentation / Q000379:methods*; D007202:Indicators and Reagents; D057230:Limit of Detection; D004364:Pharmaceutical Preparations / Q000032:analysis* / Q000592:standards; D015203:Reproducibility of Results; D052617:Solid Phase Microextraction
chemical_list: D001388:Aziridines; D005021:Ethylamines; D007202:Indicators and Reagents; D004364:Pharmaceutical Preparations; C033132:aziridine; C010076:2-chloroethylamine