Since the S/N ratio for compound A (conc. 250 ng/mL) at enhanced mass-resolution was above that required for the limit of quantitation (Figure 4), compound A was diluted by a factor of 10 (conc. 25 ng/mL) and reanalyzed. The LC/ESI-SRM chromatograms obtained using enhanced mass-resolution at the lower concentration of compound A are shown in Figure 5. A clearly-defined peak for compound A is observed which is easily quantifiable. Hence, using enhanced mass-resolution on the Finnigan TSQ Quantum Discovery, at least an order of magnitude decrease in LOQ for compound A is achieved, relative to unit mass-resolution operation, without the need for time-consuming chromatographic manipulations. Satisfactory precision and accuracy values for analytes present in plasma have been previously reported for quantitative studies on the Finnigan TSQ Quantum Discovery in enhanced mass-resolution mode.[3,4].
Previous quantitative studies using the Finnigan TSQ Quantum Discovery also found that improvement in analyte sensitivity obtained at enhanced mass-resolution, as shown here, is proportional to an increase in the linear dynamic range for the assay.[3,4,6] An extended linear dynamic range is advantageous in applications such as discovery pharmacokinetic (PK) studies to accommodate the variable concentrations of analytes in the study samples.
1. Yang L, Amad M, Winnik WM, Schoen AE, Schweingruber H, Mylechreest I, Rudewiz PJ. Rapid Commun. Mass Spectrom. 2002; 16: 2060.
2. Jemal M, Ouyang, Z. Rapid Commun. Mass Spectrom. 2003; 17: 24.
3. Xu X, Veals J, Korfmacher W. Rapid Commun. Mass Spectrom. 2003; 17: 832.
4. Hughes N, Winnik W, Dunyach JJ, Amad M, Splendore M, Paul G. J. Mass Spectrom, in press.
5. Xu X, Tucker G, Zhou Q, Veals J, Korfmacher