Measuring organic acids and inorganic anions with ion chromatography mass spectrometry

Significance of the Topic

Ion chromatography coupled with mass spectrometry (IC-MS) provides a highly sensitive, selective and robust approach to quantify both organic acids and inorganic anions across diverse sample types. This hyphenated technique outperforms conventional conductivity or UV/VIS detection by resolving and detecting low-level ionic species even in complex matrices.

Objectives and Overview

This work reviews key IC-MS applications aimed at simultaneous identification and quantification of organic acids (e.g., glycolate, acetate, propionate) and inorganic anions (e.g., fluoride, bromate, chlorate) in matrices ranging from high-purity solvents and beverages to drinking water and clinical urine samples. It illustrates method development, sample preparation strategies, and performance metrics.

Methodology and Instrumentation

The general workflow combines high-pressure ion chromatography using Metrohm Metrosep A Supp columns (2 mm and 4 mm i.d.) with suppressed conductivity detection and electrospray ionization mass spectrometry (ESI-MS). Key automated sample preparation techniques (MISP) include Inline Ultrafiltration, Inline Dialysis, Inline Matrix Elimination and the Metrohm intelligent Pick-Up Technique (MiPuT) or Partial-Loop Injection (MiPT) for precise, low-volume handling. Data acquisition and instrument control are achieved via Metrohm drivers for Waters™ Empower™ and Agilent™ OpenLab CDS software.

Main Results and Discussion

• Impurity Analysis in High-Purity Chemicals: Trace levels of weak organic acids were quantified in NMP, methanol, ethanol, 2-propanol and H₂O₂ (30%) with detection limits in the low µg/L range, unaffected by matrix interferences.
• Organic Acids and Anions in Organic Matrices: A 200 µL proprietary sample was screened for 18 analytes (fluoride, glycolate, adipate, bistriflimide, etc.) using a 55 °C gradient on Metrosep A Supp 7, achieving limits of quantification down to 5 µg/L.
• Quality Control of Beverages: A 32-minute method on Metrosep A Supp 19 separated 17 organic acids (quinate, shikimate, malate, citrate) and 7 inorganic anions; calibrations (4–200 µg/L) yielded R² > 0.997.
• Oxyhalide Impurities in Bottled Water: A 12-minute microbore (2 mm) separation quantified bromate, chlorite and chlorate at ng/L levels alongside mg/L common anions; absolute detection limits reached pg levels through volume-varied calibration with MiPuT.
• Medical Applications – Urine Analysis: Glycerate, glycolate, oxalate and citrate were determined in diluted urine with minimal chloride interference using an isocratic 60 °C run on Metrosep A Supp 19, with MS quantification in the nmol range.

Benefits and Practical Applications

• High sensitivity and selectivity for co-eluting or low-level ionic species.
• Automated, reproducible sample preparation for complex and particulate-laden matrices.
• Streamlined calibration via MiPuT/MiPT reduces reagent usage and manual effort.
• Single-run multi-analyte screening accelerates process control in pharmaceuticals, semiconductors, food & beverage and environmental laboratories.

Future Trends and Opportunities

Advancements in IC-MS are expected to include tandem MS/MS detection for enhanced selectivity, expanded inorganic cation and amine profiling, and integration with artificial intelligence for automated peak assignment. Further miniaturization of columns and refinement of inline sample prep will drive higher throughput, lower limits of detection and broader adoption in regulatory, clinical and forensic laboratories.

Conclusion

IC-MS represents a powerful multi-parameter platform for comprehensive ionic analysis. Through robust suppression, metal-free flow paths and automated Metrohm Inline Sample Preparation, the technique achieves low-level quantification of organic acids, oxyhalides and inorganic anions in a single run, supporting quality control across a wide spectrum of industries.

Used Instrumentation

• Metrohm Ion Chromatograph with Metrosep A Supp columns (150/2.0 and 250/4.0)
• Suppressor module for conductivity detection
• Single-quadrupole mass spectrometer with ESI source (Agilent InfinityLab LC/MSD or Waters Q-instrument)
• Metrohm Inline Sample Preparation (Ultrafiltration, Dialysis, Matrix Elimination)
• Metrohm intellect Pick-Up Technique (MiPuT) and Partial-Loop Injection Technique (MiPT)
• Software: Metrohm drivers for Waters Empower CDS and Agilent OpenLab CDS

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