Development of a LC-MS screening procedure for the application in analytical toxicology

Barbara Hinterberger
2012 unpublished
Systematic Toxicological Analysis is an ongoing challenge in forensic as well as in clinical toxicology. The development of new methods based on LC-MS has been in the focus of researchers during the last decade. In order to establish a routine toxicological screening, all factors influencing the procedure need to be identified. Beginning from the ionization process and acquisition settings to the reference library - multiple factors have to be evaluated. Moreover, reproducibility and
more » ... lity of spectra is another issue, yet without satisfying solution. Introduction: For the development of a screening procedure a Linear Ion Trap was used in combination with HPLC and the ToxID library. Special emphasis was put on all parameters influencing a screening, including instrument features as well as on issues evolving from the library search. The aim was to identify the main factors that have to be considered when establishing LC-MS for Systematic Toxicological Analysis based on the used linear Ion Trap. Material and Methods: The LTQ Velos (Thermo Fisher Scientific) was the MS used for this work, in combination with the RS 300 Ultimate HPLC (Dionex). A testmix with 13 toxicologically relevant substances was used for individual experiments. Deuterated standards were used to detect changes in the retention times of the chromatographic system. Single substances or a mix of compounds were either directly infused or injected via on-line HPLC. Pretests for limit of detection tests were performed for the compounds of the testmix and two real samples were analyzed with the newly established method. Screening results were evaluated manually and with ToxID - a library search tool provided by Thermo Fisher Scientific. Additionally the screening software SmileMS (GeneBio) was used. Results and Discussion: The key-parameters for the creation of library spectra and consequently for practical screening are discussed, as well as the proper ionization settings for different applications. Several methods for multi-target- and gen [...]
doi:10.25365/thesis.18846 fatcat:oafvkb7bsfd6zcsqyr6c3trmiy