International standard sensitivity enhancement

Ion suppression is so far mainly considered in the context of sensitivity and the lower limit of quantification of an assay. But it has to be emphasized that short term variations in ion yields—particularly due to matrix components—can compromise the accuracy of analyses Whenever the variation of ion yield has a differential impact on target analyte and internal standard, accuracy is compromised. This means that the reliability of LC-MS/MS analyses critically depends on (1) how similar the impact of ion suppression or ion enhancement on target analyte and internal standard compound is and on (2) how similar the matrices of calibrator samples and actual patients samples are with respect to the modulation of ionization efficacy. This problem can be of relevance for an entire measuring series—if systematic differences in the ionization modulation properties of calibration materials and actual patients samples are present—or it may non-systematically affect individual patients samples as well. 

The combination provides enhanced sensitivity, selectivity, speed of analysis, an opportunity for automation, feasibility of quantification of coeluting components or isobaric compounds, and use of the stable-isotope labeled analogs as internal standards. 

Even though addition of stable isotope labeled internal standards is useful for quantitation, in SIM mode both analytes and internal standards co-elute. Further, enhanced specificity and sensitivity were achieved by using a tandem mass spectrometer (MS/MS), operated in selected reaction monitoring (SRM) mode to monitor isolated folate-specific ion fragmentation [15,26,33]. 

LC-MS/MS instrnment parameters are shown in Table 3. Compound specific parameters are shown in Table 4. The acquisition file is divided into separate functions in which the number of SRM transitions monitored is minimized. This provides enhanced sensitivity since the mass spectrometer does not scan the SRM transitions for every compound during the entire run. One isotopically labeled compound is chosen as internal standard for every function. 

Guerra et al. [139] developed an LC linear ion-trap MS/MS method to measure TBBPA and BDEs at ultratrace levels with limits of detection below 1 pg. The authors compared selected reaction monitoring with enhanced product-ion (EPI) MS approaches and observed slight improvements in sensitivity with the EPI method. These methods were then applied to the analysis of sludge and sediment samples [140]. Bacaloni et al. [141] developed a LC—APPI—MS/MS method for both TBBPA and BDEs in water samples. Matrix effects were not observed for these samples, and quantitation was based on external calibration. Morris et al. [142] measured TBBPA and HBCDs in aquatic samples by LC—ESI—MS, using an isotopically labeled internal standard for TBBPA determinations. Tollback [143] developed a rapid LC—ESI—MS method for the determination of TBBPA in air samples, also based on the use of an isotopically labeled internal standard. TBBPA could be determined at levels 30 to 40 times lower with ESI than with APCI. Hayama et al. [144] describe a method for determination of TBBPA in hmnan serum samples by LC—ESI—MS/MS, also based on an internal standard calibration approach. 

The characteristics of solid headspace sampling with an internal standard for the determination of residual volatiles in polymers are given in Table 2.45. Generation of a headspace sample is an equilibrium process that limits the amount of a specific component available for analysis within the practical restraints of time and temperature. Static headspace sampling in atmospheric conditions is limited to about 210°C (oxidation and thermal decomposition of polymers) an alternative is thermo desorption in inert conditions. Sensitivity is enhanced by 100 times using LVI with on-column cry-ofocusing. Solid headspace provides about 10-fold more sensitivity than solution headspace. HS-GC does not suffer from interference fl om the solvent peak or from impurities. Typical detectors used in SHS-GC are FID, BCD and MS. Determination of... 

FEWS sensors are similar to ATR spectrometers however, unlike standard ATR crystals, the elongated configuration of the fiber ensures a longer waveguide/medium. This in turn generates a larger number of internal reflections, thus enhancing detection sensitivity. 

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