Determination of Iodinated Contrast Media in Aqueous Samples by Direct-Injection LC-MS/MS

Importance of the topic

Iodinated contrast media (ICMs) are routinely used in medical imaging and enter aquatic environments via hospital effluents and wastewater treatment plants. Due to their high polarity and persistence, ICMs often remain unremoved by conventional treatment processes, leading to trace level contamination of surface water, groundwater, and drinking water. Accurate, sensitive detection of individual ICMs at ng/L (ppt) levels is critical for environmental monitoring, risk assessment, and management of water quality.

Objectives and Study Overview

This work aimed to develop and validate a direct-injection LC-MS/MS method for seven commonly used iodinated contrast agents (iopamidol, ioxitalamic acid, iohexol, iomeprol, diatrizoic acid, iopromide, ioxaglic acid) in aqueous samples. The focus was on achieving low ppt limits of detection without extensive sample preparation, evaluating precision, linearity, and recovery in tap water, surface water, and wastewater treatment plant effluents.

Methodology and Instrumentation

This method employed an Agilent 1290 Infinity II LC system with a 100 µL analytical loop and an Agilent ZORBAX Eclipse Plus C18 RRHD column (2.1 × 150 mm, 1.8 µm) held at 15 °C. The mobile phases were 0.1 % acetic acid in water (A) and acetonitrile (B), delivered at 0.4 mL/min with a 7-minute gradient from 0 % to 95 % B. Sample injection volume was 100 µL after simple filtration. Detection was performed on an Agilent 6495 Triple Quadrupole MS with Jet Stream electrospray in positive mode, using dynamic multiple reaction monitoring (MRM) transitions optimized for each analyte and isotopically labeled internal standards.

Key Results and Discussion

• Limits of detection ranged from 1 to 10 ppt, with linear calibration (1–1 000 ppt) and R² ≥ 0.996 for all compounds.
• Intra-day precision (n=5) gave RSD < 10 % at 20 and 200 ppt levels.
• Chromatographic separation achieved sharp, symmetric peaks and resolved isomeric pairs (iopamidol/iomeprol).
• Recoveries for spiked samples (200 ppt) in tap, surface, and effluent waters generally fell between 75 % and 125 %, demonstrating minimal matrix bias, except where ion suppression affected compounds lacking matching internal standards.

Benefits and Practical Applications

• Eliminates time-consuming solid-phase extraction and reduces solvent consumption.
• Direct injection streamlines workflow, lowers cost per analysis, and minimizes potential sample handling errors.
• Achieves ppt-level sensitivity, enabling routine monitoring of ICMs in environmental and wastewater laboratories.

Future Trends and Potential Applications

• Expansion to include a wider range of pharmaceutical and transformation products using high-resolution MS.
• Integration with online sample enrichment or micro-flow LC for enhanced sensitivity.
• Automated data processing and suspect screening workflows for rapid identification of emerging contaminants.
• Application to other challenging polar compounds in clinical, environmental, and industrial settings.

Conclusion

The direct-injection LC-MS/MS approach described offers a fast, reliable, and highly sensitive solution for quantifying iodinated contrast agents in water. By combining efficient chromatographic separation with triple quadrupole detection, the method meets stringent environmental monitoring requirements with minimal sample preparation.

References

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