Forensic Science by M.J. Bogusz

Author:M.J. Bogusz [Bogusz, M.J.]
Language: eng
Format: epub
Publisher: Elsevier, Inc.
Published: 2008-10-16T04:00:00+00:00

14.5.3 Screening based on accurate mass measurement

TOF-MS is the third common alternative for the multicomponent drug screening of biological samples. Accurate mass measurements are used to determine the elemental composition of all ions of interest in the sample. The calculation of possible molecular structures facilitates the screening of genuine unknowns by comparing the calculated structures to those in electronic databases, which essentially are lists of accurate masses and names of the corresponding chemical compounds. TOF instruments provide relatively high mass accuracy (∼5 ppm) and reasonable resolution (5000–10000 fwhm) and have been used in combinatorial chemistry and in the analysis of drugs and their metabolites.

In single-MS TOF instruments (single-MS TOF), quadrupoles focus the ion beam on the TOF analyser, which is positioned perpendicularly, and ions are pulsed into the flight tube by applying voltage. The ions separate according to their m/z values, as high-mass ions have longer flight times. A quadrupole instrument (QTOF) is a hybrid mass spectrometer with MS/MS capability. The quadrupole operates as an ion guide in MS mode and is used for selecting parent ions in MS/MS mode. A collision cell is located between the quadrupole and the TOF analyser to induce fragmentation in MS/MS experiments.

Comprehensive target screening methods have been reported both for single-MS TOF [43,44] and QTOF instruments [45–47]. A typical concept is to screen over the desired mass range (e.g. m/z 100–700) with a single-MS in full scan mode. Based on these acquired accurate masses, the elemental composition of detected peaks can be calculated and searched against an electronic target database, such as the Merck Index[47] or the laboratory’s own list of relevant compounds and their accurate masses [43,44]. Thus, the compounds can be tentatively identified without reference compounds. Using single-MS TOF instruments, a mass accuracy of 5–10 ppm has been reported for the majority of drugs in authentic samples [44]. If a metabolic pattern for detected drugs is used as an additional criterion, a mass window of 20 ppm in real urine samples was considered sufficient to detect the correct findings, and, with the use of dedicated software, to rule out apparent false–positive findings [43,44]. In a further development of the method, mass spectral identification was based not only on matching measured accurate masses, but also on the isotopic pattern (SigmaFit) match between the sample component and the theoretical values in the database. A new generation TOF instrument allowed the use of a mass window as narrow as ±10 ppm in screening [48]. By using accurate masses, even single-MS TOF instruments enable a large number of toxicants to be screened during a single injection without sacrificing sensitivity or selectivity. One limitation, set by the user, is the selection of compounds in the database. Some complexity in interpreting the results stems from the fact that two or even more drugs are often obtained for the same molecular formula. The number of candidates differing by formula can be further decreased by using an instrument with higher mass accuracy (e.g. FTMS). In any case, retention time is a necessary criterion for identification.

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