Purchasing the Right Mass Spectrometer: Triple Quadrupole vs. HRAM

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Purchasing the Right Mass Spectrometer: Triple Quadrupole vs. HRAM

Team TFS
Team TFS

In my last blog post, “Purchasing the Right LCMS: Lessons Learned from Wedding Planning” I encouraged you to think through a couple of key questions around your LCMS instrument purchasing goals. In today’s blog post, I will walk us through the differences between Triple Quadrupole and High-Resolution Accurate Mass Spectrometry (HRAM) instruments. Keep your answers to the questions from the last post handy!

shutterstock_198156971For starters, if you are looking to only perform targeted quantitation with ultimate sensitivity being important, triple quadrupole mass spectrometry (MS) instruments are the best option. If your primary focus today is performing untargeted screening of your analytes, HRAM technology would be the most suitable. However, you may find that your goals fall somewhere in between, where either technology could be an option as depicted in the table below. Please note: The table does not include Ion Trap Mass Spectrometry, which could also meet your analytical needs as a general-purpose mass spectrometer for both screening and quantitation.

So how do you choose?



Triple quadrupole LCMS instruments are known to provide ultimate sensitivity using selected-reaction monitoring (SRM) mode. They are tandem quadrupole mass analyzers with two mass analyzers (referred to as Q1 and Q3) which act as double mass filters. The q2 is a collision cell. With new, higher-end instruments providing high resolution selected-reaction monitoring (H-SRM) mode, they also enable enhanced selectivity by increasing the width of Q1 and Q3 which is beneficial in analyzing complex matrices. The SRM mode also enables reliable analysis of large quantities of samples and the short dwell times permit detection of multiple different transitions.

Although triple quadrupole instruments provide the highest sensitivity for targeted quantitation, HRAM MS instruments should be considered when quantifying low molecular weight compounds in complex samples. HRAM instruments provide market-leading resolving power to separate ions of interest from matrix ions, providing improved selectivity. These Orbitrap mass analyzers/detectors include a central electrode that has two outer electrodes wrapped around it. One of the reasons that these instruments provide superior resolution is due to the accuracy (nanometer range) of the electrodes. You also do not have to perform compound optimization every time you add a new target to your list.


HRAM instruments can perform both untargeted and targeted screening. During screening mode, the instrument analyzes retention time, isotopes, fragment ions and exact mass. You would be able to import the mass spectra with isotopic patterns into a library search. In addition to resolving ions of interest from the background, high-resolution instruments can also differentiate between analytes that are similar structurally by determining the elemental composition of individual fragment ions which is a key advantage. Lastly, HRAM instruments can achieve mass accuracy at or below ppm levels.

For unknown compound identification following screening,  the Thermo Scientific Compound Discoverer Software matches fragmentation spectra against the mzCloud™ spectral library, the world’s largest and most curated mass spectral library. You can always use ChemSpider™ as well if you want to search by molecular weight or formula. Furthermore, Thermo Scientific™ mzVault™ allows you to build a database for an application area of interest to you. The mzLogic data analysis algorithm will combine spectral library similarity searches with chemical databases so you can rank and propose the best unknown candidates. These are exceptional tools in your journey to identify unknowns!

Triple quadrupole MS instruments can perform targeted screening using only pre-defined lists of analytes. If your lab anticipates a need to investigate new analytes in the same samples, HRAM MS instruments uniquely enable retrospective analysis because they collect data on all analytes in the sample!

Both technologies will deliver robustness, reproducibility and reliability required for your application. As should be apparent, deciding which technology to purchase really depends on the goals of your application for today and tomorrow, as well as meeting the profitability goals for your organization.

Learn More

What makes Orbitrap mass spectrometry the first choice for both routine and research applications?

When Should You Walk on the Path to More Confident Quantitation?