MSACL Conference Schedule

Mass Spectrometry in Toxicology: Broad Spectrum Drug Screening with Quadrupole and Ion Trap Mass Spectrometry
Wed 8:00 AM - Session: Toxicology
Kara Lynch
The use of LC-MS and MS/MS for broad spectrum drug screening in clinical laboratories has developed rapidly since 2000. Initial studies established that spectra generated with electrospray ionization followed by in-source fragmentation (single stage mass analysis) or product ion scans (tandem mass analysis) could be used for reliable identification, although spectral libraries may be not be transferable between instruments from different vendors. Current work is directed towards characterizing the relative ability of different mass analyzers and acquisition strategies to identify toxins from the complex matrix and drug/metabolite mixtures represented by patient samples encountered in the clinical workload.

It is challenging to accurately assess false negative and false positive rates in such studies because of the heterogeneous, multi-component nature of the methods (e.g. differing drug menus of several hundred compounds) and the lack of any consensus on clinical goals or reference method(s). Despite these difficulties, it is still important to perform comparative studies such that the reproducibility, robustness, analytical sensitivity and specificity, and fitness for clinical purpose of differing LC-MS or MS/MS techniques can be evaluated using accepted method validation principles.

To illustrate these issues we will discuss the results, value, and limitations of a collaborative study by the clinical laboratories at Johns Hopkins University Medical Center and San Francisco General Hospital/UCSF in which 100 patient urines were tested with three different LC-MS or MS/MS drug screening techniques. Drug detection capabilities of the LC-MS or MS/MS methods for this specimen set were also compared to a GCMS method, to HPLC-UV (BioRad Remedi