Tomorrow's quantitation

Importance of Topic

Advances in quantitative mass spectrometry are crucial across food safety, environmental monitoring, clinical research, forensic toxicology, and pharmaceutical discovery. Liquid chromatography coupled with triple quadrupole (LC-QQQ) and high-resolution accurate mass (HRAM) hybrid quadrupole-Orbitrap mass spectrometers provide complementary strengths in sensitivity, selectivity, speed, and data-rich workflows. Robust quantitative assays ensure compliance with regulatory limits, protect public health, and enable retrospective analysis of complex samples.

Objectives and Study Overview

This review summarizes recent developments in targeted and untargeted quantitation using LC-QQQ and HRAM instruments. It covers applications in:

• Food safety testing: pesticides, veterinary drugs, mycotoxins, biotoxins, dyes, and adulterants in diverse matrices
• Environmental contaminants analysis: per- and polyfluoroalkyl substances, cyanotoxins, disinfection by-products, pharmaceuticals and personal care products in water
• Clinical research and forensic toxicology: synthetic hormones and illicit substances
• Pharmaceutical discovery: multiclass workflow integration and high-throughput screening

The goal is to compare methodology, performance metrics, software integration, sample throughput, and future directions.

Methodology and Instrumentation

Sample preparation approaches include QuEChERS, solid-phase extraction (SPE), ion chromatography (IC), direct injection, and laser diode thermal desorption (LDTD-APCI). Data acquisition modes span:

• Selected reaction monitoring (SRM) and high-resolution SRM (H-SRM) on triple quadrupole MS
• Full-scan HRAM with data-dependent MS/MS (FS-ddMS2), targeted precursor selection (tSIM/PRM), all-ion fragmentation (AIF), and variable data-independent acquisition (vDIA)

Key instrumentation platforms include:

• Thermo Scientific TSQ Quantis, TSQ Altis, and TSQ Fortis triple quadrupole mass spectrometers
• Thermo Scientific Q Exactive, Q Exactive Focus, and hybrid quadrupole-Orbitrap high-resolution mass spectrometers
• Liquid chromatography systems: Vanquish Flex UHPLC, UltiMate 3000 RSLC, Dionex ICS-5000+ Hybrid HPIC
• Software tools: TraceFinder, Chromeleon CDS, Compound Discoverer, mzVault spectral libraries, ToxID screening

Main Results and Discussion

• Triple quadrupole MS delivers sub-ppb to ppt sensitivity for targeted quantitation, with fast dwell times and high throughput (70–100 injections/day) in complex matrices such as chili powder, fruits, vegetables, and grains.
• HRAM Orbitrap MS achieves superior resolving power (up to 70,000 FWHM), enabling separation of isobaric interferences, retrospective full-scan data re-interrogation, and elemental composition determination. Limits of detection often reach low ng/kg or ng/L levels, with mass accuracy <5 ppm.
• Hybrid HRAM workflows allow simultaneous quantitation, confirmation, and non-targeted screening of hundreds of compounds in a single injection, reducing method development time and increasing laboratory productivity.
• IC-MS/MS provides a derivatization-free approach for polar analytes such as perchlorate, haloacetic acids, and polar pesticides, meeting regulatory monitoring requirements with low-ppt detection.
• Remote instrument monitoring (Almanac app) and enterprise software eWorkflows streamline instrument management, data acquisition, processing, and reporting under regulated conditions (GLP/GMP, 21 CFR Part 11).

Benefits and Practical Applications

• High sensitivity and selectivity ensure reliable compliance with EU, EPA, FSSAI, and other global regulations.
• Flexibility to switch between targeted SRM quantitation and broad HRAM screening supports current and future analyte panels.
• Retrospective data analysis captures unknown or emerging contaminants without re-running samples.
• Integrated software platforms simplify method creation, data processing, reporting, and remote laboratory oversight.
• Rapid turnaround supports food, environmental, and clinical laboratories with high sample loads and tight deadlines.

Future Trends and Potential Applications

• Wider adoption of HRAM for combined targeted and untargeted workflows, including suspect screening and non-targeted discovery.
• Expansion of compound databases and spectral libraries for emerging contaminants such as novel pesticides, pharmaceuticals, and biotoxins.
• Integration of machine learning in data processing for automated feature recognition, quantitation, and structural elucidation.
• Increased use of passive and on-line sampling techniques coupled to HRAM for continuous environmental monitoring.
• Greater networked laboratory management with eWorkflows, remote diagnostics, and cloud-based data sharing.

Conclusion

The synergy of LC-QQQ and HRAM mass spectrometry, combined with advanced sample preparation, acquisition modes, and software, empowers laboratories to tackle a wide range of quantitative challenges. Selecting the optimal technology depends on sensitivity, selectivity, flexibility, and budget. As instrument performance and data-processing tools evolve, comprehensive targeted and non-targeted workflows will become routine, meeting the demands of food, environmental, clinical, forensic, and pharmaceutical analysis.

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