Tandem Mass Spectrometry: Rising to Challenges in Clinical Labs

Following SCIEX’ launch of a new tandem mass spectrometry system, we spoke with Michael Jarvis, Product Manager at SCIEX, to find out more.

The Citrine™ MS/MS system offers a unique combination of sensitivity and speed, and enables trace level analysis, quantification of comprehensive panels of compounds, and the measurement of both large and small molecules, across a wide range of concentrations.

In addition, the QTRAP® technology enables unique workflows, providing quantitative and qualitative analysis in a single injection.

Can you tell us about some of the innovative technologies that make up the Citrine QTRAP MS/MS? 

There are three exclusive capabilities that I would like to highlight with respect to the Citrine QTRAP: the scanning speed, the enhanced sensitivity, and the ability to perform second-order fragmentation. The QTRAP can achieve scanning speeds up to 20,000 Da/s, much faster than conventional triple quadrupole mass spectrometers. This accelerated analysis speed is particularly useful for obtaining full-scan MS/MS spectra. Typically acquiring these spectra is time-consuming and can compromise a laboratory’s ability to simultaneously collect good quantitative data. However, the rapid scanning speed of the Citrine QTRAP MS/MS allows the collection of quantitative and qualitative data in a single injection.

The QTRAP is also exceptionally sensitive. When a conventional triple quadrupole mass spectrometer performs a scan across a range of masses, only a single mass is allowed to pass through the quadrupole mass filter and reaches the detector at any point during the scan. This means that all of the ions below and above the currently selected mass are lost, which results in a dramatic reduction in sensitivity. With a QTRAP system, ions can be trapped and accumulated in the linear ion trap region. When a scan is performed, ions are sequentially scanned out of the QTRAP in a mass-selective manner and no ions are lost. Simplistically, this means that we can obtain highly sensitive MS/MS spectra, even when scanning very rapidly across a wide mass range.

The ability to trap fragment ions in the QTRAP also provides an opportunity to perform second order fragmentation, often referred to as MS/MS/MS, or MS3. In such an experiment we can isolate a first-generation fragment ion in the linear ion trap region, do further fragmentation on that particular ion to generate a second generation of ions, and then sequentially scan the secondary fragment ions out of the QTRAP to the detector. This approach can be particularly helpful for differentiating between compounds having the same mass and similar structures, and will usually eliminate most chromatographic interference peaks. On a conventional triple quadrupole MS, the resolution of these interference peaks would usually require increased chromatographic run-time, but the Citrine QTRAP eliminates this need.

What makes the Citrine MS/MS system particularly suited to meet the needs of clinical labs? Especially the demands of endocrine applications?

Sensitivity continues to be a driver in clinical applications and with the Citrine MS/MS system we can measure challenging hormones at low pg/mL concentrations, from a variety of biological fluids. Additionally, there is a growing need to measure large panels of structurally similar steroids, sometimes hundreds of compounds in the same analysis, for the purposes of profiling to understand changes over time. In order to provide a time-effective analysis without compromising data quality, it’s crucial to use exceptionally fast instrumentation.

The Citrine MS/MS system can be operated in either Electrospray Ionization (ESI) or Atmospheric Pressure Chemical Ionization (APCI) mode. This versatility allows users to address the widest range of analytes, and the APCI mode is particularly useful for the ionization for non-polar compounds such as steroids. Without using any tools, we can easily and rapidly switch between ESI and APCI modes in a matter of seconds.

In addition to first-rate sensitivity and speed, I would say that the very large linear dynamic range of the Citrine MS/MS system is a critical feature for endocrinologists. A large linear dynamic range means that a given LC-MS/MS method can accurately quantify target compounds over a wider range of concentrations, without requiring samples to be diluted and reanalyzed.

What do you see for the future for mass spec in clinical applications and healthcare? What other applications is it likely to positively impact?

Besides the significant impact in fields where speed and sensitivity are required, I would say in general that only mass spec has the necessary specificity to accurately differentiate between similar compounds, particularly at low concentrations. As an example, an immunoassay can accurately measure testosterone in the ng/mL concentration range. But when levels of testosterone are very low, for example in the pg/mL concentration range, it is common for an immunoassay to overestimate the concentration by as much as 200-300% due to cross-reactivity with other steroids, rendering the measurement meaningless. Because immunological methods are based on antibody specificity they will always present cross-reactivity and interference to some extent. Since mass spectrometry is allowing us to see exactly what it is we’re measuring, it is widely becoming regarded as the gold standard for high quality, highly accurate measurements. If you are trying to make a diagnosis based on your measurements, it’s essential that they are accurate.

The key to success, and to the widespread adoption of mass spec in the clinical lab, is to shorten the analysis and processing time to be competitive with traditional laboratory techniques such as immunoassay. This will improve the productivity of laboratories that employ mass spectrometry for high throughput assays.

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Michael Jarvis was speaking to Anna MacDonald, Science Writer for Technology Networks.