title: Reliability of veterinary drug residue confirmation: high resolution mass spectrometry versus tandem mass spectrometry.
abstract: Confirmation of suspected residues has been a long time domain of tandem triple quadrupole mass spectrometry (QqQ). The currently most widely used confirmation strategy relies on the use of two selected reaction monitoring signals (SRM). The details of this confirmation procedure are described in detail in the Commission Decision 93/256/EC (CD). On the other hand, high resolution mass spectrometry (HRMS) is nowadays increasingly used for trace analysis. Yet its utility for confirmatory purposes has not been well explored and utilized, since established confirmation strategies like the CD do not yet include rules for modern HRMS technologies. It is the focus of this paper to evaluate the likelihood of false positive and false negative confirmation results, when using a variety of HRMS based measurement modes as compared to conventional QqQ mass spectrometry. The experimental strategy relies on the chromatographic separation of a complex blank sample (bovine liver extract) and the subsequent monitoring of a number of dummy transitions respectively dummy accurate masses. The term "dummy" refers to precursor and derived product ions (based on a realistic neutral loss) whose elemental compositions (CxHyNzOdCle) were produced by a random number generator. Monitoring a large number of such hypothetical SRM's, or accurate masses inevitably produces a number of mass traces containing chromatographic peaks (false detects) which are caused by eluting matrix compounds. The number and intensity of these peaks were recorded and standardized to permit a comparison among the two employed MS technologies. QqQ performance (compounds which happen to produce a response in two SRM traces at identical retention time) was compared with a number of different HRMS(1) and HRMS(2) detection based modes. A HRMS confirmation criterion based on two full scans (an unfragmented and an all ion fragmented) was proposed. Compared to the CD criteria, a significantly lower probability of false positive and false negative findings is obtained by utilizing this criterion.
authors.affiliation: Official Food Control Authority of the Canton of Zurich, Fehrenstrasse 15, 8032 Zürich, Switzerland. Electronic address: anton.kaufmann@klzh.ch.
authors.forename: A
authors.initials: A
authors.lastname: Kaufmann
authors.affiliation: Official Food Control Authority of the Canton of Zurich, Fehrenstrasse 15, 8032 Zürich, Switzerland.
authors.forename: P
authors.initials: P
authors.lastname: Butcher
authors.affiliation: Official Food Control Authority of the Canton of Zurich, Fehrenstrasse 15, 8032 Zürich, Switzerland.
authors.forename: K
authors.initials: K
authors.lastname: Maden
authors.affiliation: Official Food Control Authority of the Canton of Zurich, Fehrenstrasse 15, 8032 Zürich, Switzerland.
authors.forename: S
authors.initials: S
authors.lastname: Walker
authors.affiliation: Official Food Control Authority of the Canton of Zurich, Fehrenstrasse 15, 8032 Zürich, Switzerland.
authors.forename: M
authors.initials: M
authors.lastname: Widmer
mesh_terms: D016477:Artifacts; D004350:Drug Residues / Q000032:analysis* / Q000737:chemistry; D005188:False Negative Reactions; D005189:False Positive Reactions; D008970:Molecular Weight; D012015:Reference Standards; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry / Q000379:methods* / Q000592:standards; D019155:Veterinary Drugs / Q000032:analysis* / Q000737:chemistry
chemical_list: D019155:Veterinary Drugs
keywords: Commission Decision 93/256/EC; Confirmation; Food safety; High Resolution mass spectrometry; Residue