Final ProgramCPSA 2011
Science and Technology Coming Together to Make a Difference
October 3 - 6, 2011
Bucks County Sheraton Hotel
Langhorne, PA
Poster Abstract #20
Comparison of Accurate Mass and Nominal Mass MSMS for the Simultaneous Acquisition of Qualitative and Quantitative Data in DMPK Studies
Waters Corporation, Milford, MA, USA
A crucial phase of the drug discovery process is quantitative and qualitative analysis of candidate pharmaceuticals and their metabolites in biological fluids. Typically, a triple quadrupole (TQ) mass spectrometer is used for quantitative analysis, while qualitative data is derived from hybrid quadrupole time of flight (QToF) or ion trap instrumentation. In this study, compare the benefits and drawbacks for the simultaneous acquisition of qualitative and quantitative LC/MS/MS data using either a QToF or a TQ instrument. The throughput, sensitivity, and spectral quality were compared using 20 structurally diverse compounds in blood products.
The TQ mass spectrometer was used to simultaneously acquire LC/MS data in MRM mode for quantitative analysis and full scan mode for qualitative analysis of metabolites. The QToF was operated in alternating low and elevated energy mode allowing simultaneous collection of precursor and product ion data. QToFs can acquire data at fast acquisition speeds without reduction in mass accuracy or spectral quality, allowing a narrow mass window for data processing. This feature allowed use of a 0.5mDa mass window around the target analytes thereby offering a high degree of selectivity and excellent signal with 50pg/mL standards. The use of new detector electronics allowed for stable mass measurements and a wide dynamic range.
The average limits of detection (LOD) for the TQ mass spectrometer in MRM mode was ~10pg/mL while that of the QToF was ~50pg/mL for all 20 compounds. The fast data capture rate of the TQ mass spectrometer ensured that the LOD was not changed by the use of very fast gradient analysis. Compared to the 5 mins gradient, the QToF LOD was reduced ~5 fold with 2 minute gradients owing to the faster sampling rate affecting the ion statistics. Whilst the TQ mass spectrometer was more sensitive for quantitation, the full scan data used for metabolite detection with this instrument was ~50 times less sensitive than the QToF data. The QToF also provides more spectral information than the TQ mass spectrometer. Both instruments were found to be ideal for DMPK studies, with the TQ mass spectrometer being better for high throughput quantitation.
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