Targeted and Non-Targeted Screening for Drugs

Overview

The high resolution and accurate mass AB SCIEX TripleTOF™ 4600 LC/MS/MS system was used to screen for drugs from forensic equine urine, and to quantify drug compounds with excellent accuracy and high reproducibility. Fast Information Dependent Acquisition (IDA) MS/MS spectra were used to additionally confirm the identity of detected compounds based on mass spectral library searching. The acquired full scan MS and MS/MS data can further be used in a general unknown comparative screening workflow in which a sample-control comparison can be made for easy, fast and reliable identification of compounds present in the sample.

PeakView^® software with the XIC Manager add-in was used for targeted and non-targeted data processing. The XIC Manager manages large lists of compounds and performs extracted ion chromatogram (XIC) calculations, both targeted and non-targeted peak finding operations and library searching. The XIC Manager allows the ability to review results based upon retention times, accurate mass, isotopic pattern and MS/MS library searching. The PeakView^® software can further be used to aid in the formula and structural elucidation, elemental composition determination and fragmentation interpretation to confidently identify unknowns.

Figure 1 AB SCIEX TripleTOF™ 4600 System

Introduction

Liquid Chromatography coupled to Tandem Mass Spectrometry (LC-MS/MS) is a widely used analytical tool for the screening of drugs. Triple quadrupole based mass analyzers operated in Multiple Reaction Monitoring (MRM) mode deliver highly selective and sensitive quantitative results, but are limited to targeted screening only. With an increasing demand for retrospective and non-targeted analyses, full scan mass analyzers are gaining popularity. The AB SCIEX TripleTOF™ 4600 LC/MS/MS system is a hybrid quadrupole/ time-of-flight (QqTOF) instrument with unmatched speed in acquisition of highly sensitive full scan MS spectra with high resolution and mass accuracy allowing accurate and reproducible quantification of targeted compounds. In addition, the unmatched speed of the TripleTOF™ 4600 LC/MS/MS system allows 20-30 Information Dependent Acquisition (IDA) MS/MS spectra to be collected for confident compound identification based on MS/MS library searching and/or structural elucidation determinations. This allows the capability to perform targeted and non-targeted screening in a single LC-MS/MS run reducing the possibility of missing the detection of compounds. The complexity of such data requires powerful data mining tools. The XIC Manager can be used for target and non-targeted processing of high resolution MS and MS/MS data allowing for screening and identification with the highest confidence based on retention time, accurate mass molecular ion, isotopic pattern and automatic MS/MS library searching. The acquired full scan MS data can further be used to retrospectively mine data for non-targeted compounds. The information of the accurate mass molecular ion, isotope pattern and detected fragment ions can be used to characterize the structure of unexpected compounds using features of the PeakView^® software. Formula Finder can be used to determine the empirical formula and Fragment Ion Prediction for determining the proposed structure. Here we present examples of using the AB SCIEX TripleTOF™ 4600 system for the screening and identification of drugs in equine urine. Features of the XIC Manager for targeted and non-targeted screening are highlighted.

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