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Application Notes

A New High Sensitivity Tandem Quadrupole Mass Spectrometer for Quantitative LC/MS/MS Analysis of Low Exposure Pharmaceuticals - ADVERTISEMENT

Robert S. Plumb1
1Pharmaceutical Business Operations, Waters Corporation

Abstract

The quantification of trace levels of any analyte in a complex matrix requires a highly selective and specific detector. The Waters Xevo™ TQ-S is a new high performance tandem quadrupole mass spectrometer, equipped with new StepWave™ Technology, allowing unprecedented levels of sensitivity and spectral quality.

The detection of trace levels (pg/mL) of analytes such as pharmaceuticals, metabolites, pollutants or toxins in complex matrices such as plasma, blood, or foodstuffs plays a critical role in ensuring drug and food safety. When operated in multiple reaction monitoring, or MRM, mode, LC/MS/MS has proven to be the technique of choice with exceptional selectivity, specificity and sensitivity.

As the mass spectrometry system's sensitivity is a balance between the signal from the ion(s) of interest and the signal from the unwanted background noise (the signal-to-noise ratio), the overall sensitivity depends on the instrument's efficiency of the ion sampling in the ion source and the transfer optics. Ion sampling is a delicate balance between having a large enough orifice to maximize the sampling of the ions in the electrospray source, but not too large to compromise the overall vacuum in the system. However, the source sampling process draws not only charged ions, but neutral species into the mass spectrometer vacuum region. These must first be separated from the charged ions. This process is performed in the original ion guide where the ions first enter into the MS, and is normally achieved by a hexapole-type system.

The new Waters Xevo™ TQ-S Mass Spectrometer is equipped with a novel StepWave™ ion guide. This ion guide provides an offset path via which desired ions can travel via an electrostatic charge. The unwanted, uncharged background neutral compounds are not able to make it through the offset ion path, and are exhausted to waste. This new process maximizes the ion sampling efficiency, leading to lower levels of sensitivity.

Here, it will be demonstrated how the Xevo TQ-StepWave Technology can increase the sensitivity for the analysis of low-exposure pharmaceuticals and their metabolites in plasma and blood samples.

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