Tandem Quadrupole [Mass Spectrometry]

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Glossary

WHAT IT IS

Tandem Quadrupole Mass Spectrometry (MS/MS) is an analytical technique that utilizes two mass-filtering quadrupoles separated by a collision cell to isolate, fragment, and detect ions. 

HOW IT WORKS

Quadrupole 1 (Q1) – Acts as the first mass filter, selecting a precursor ion based on its mass-to-charge ratio (m/z) from a mixture of ions produced in the ion source.

Quadrupole 2 (q2) – Functions as a collision cell, where the selected precursor ion collides with an inert gas (e.g., argon or nitrogen), causing collision-induced dissociation (CID) and generating product (fragment) ions.

Quadrupole 3 (Q3) – Analyzes the product ions by scanning or filtering specific m/z values, allowing detection and quantification of target compounds.

ADVANTAGES

Exceptional Specificity: By targeting predefined precursor-product ion transitions, MS/MS eliminates background noise and matrix interferences.

High Sensitivity: Ideal for detecting trace levels of target analytes in complex matrices such as blood, soil, water, or food.

Robust Quantification: Capable of highly accurate and reproducible measurements across a wide dynamic range, essential for regulated testing environments.

Well-Established in Method Validation: Used extensively in standard methods and regulatory guidelines (e.g., FDA, EPA, ICH) due to its reliability.

CHALLENGES AND LIMITATIONS

Targeted Analysis Only: Best suited for known analytes; does not perform untargeted screening or high-resolution exact mass detection.

Limited Structural Information: While fragmentation data can confirm identity, it is less detailed than techniques such as ion trap or Orbitrap MS.

Unit Mass Resolution: Cannot resolve closely spaced isobars unless product ions are unique.

Method Development Requirements: Transition optimization (precursor/product ions, collision energies) is needed for each analyte.

Maintenance and Calibration: Regular cleaning of ion optics and tuning are necessary to maintain optimal sensitivity and accuracy.