Fast and sensitive analysis of drug residues in water using on line SPE-UHPLC-MS/MS with ultra-fast polarity switching

Significance of the Topic

Monitoring of pharmaceutical residues in drinking and surface water is critical due to environmental and public health concerns. Increasing analytical requests and the absence of uniform regulatory limits demand methods with high sensitivity, broad compound coverage and rapid turnaround.

Objectives and Study Overview

The study aimed to develop a simple, fast and cost-effective automated workflow for screening and quantifying a diverse set of drug residues at sub-ng/L levels in various water matrices using online solid phase extraction coupled to UHPLC-MS/MS with ultra-fast polarity switching.

Methodology and Instrumentation

Key components:

• Online SPE-UHPLC system: Shimadzu Nexera X2 with low-pressure on-line SPE and high-pressure UHPLC.
• SPE cartridge: Spark Holland Oasis HLB (15 µm, 10×2 mm) at room temperature.
• UHPLC column: Restek Raptor C18 (2.7 µm, 100×2 mm) at 30 °C.
• Mobile phases: water/methanol mixtures with 0.05% NH4OH; SPE solvents included water, methanol and methanol/isopropanol.
• Flow rates: SPE loading 2 mL/min, elution 0.4 mL/min, cleaning 3 mL/min; UHPLC 0.5 mL/min.
• Injection: 1000 µL sample at 5 °C.
• MS detection: Shimadzu LCMS-8050 with heated ESI, 400 °C interface, polarity switching in 5 ms, quantitation by MRM at 5–30 ms dwell times.

Main Results and Discussion

From 130 target compounds, 40 were evaluated for sensitivity and matrix effects. Calibration (0.1–100 ng/L) in spiked spring water yielded LOQs between 0.1 and 5 ng/L. Most analytes showed acceptable accuracy (≥70–120%) and minimal matrix suppression/enhancement in spring, tap and surface water without internal standard correction. A representative chromatogram demonstrated clear baseline separation of compounds at 10 ng/L in surface water.

Benefits and Practical Application

This automated online SPE-UHPLC-MS/MS method achieves low-nanogram per liter quantification using only 1 mL samples, ensures high throughput (<14 min per run), broad analyte coverage and simplifies routine monitoring in environmental laboratories.

Future Trends and Opportunities

Ongoing efforts focus on incorporating selected isotope-labeled standards to further improve quantitation accuracy. The approach can be extended to additional emerging contaminants, adapted to regulatory guidelines and integrated into large-scale monitoring programs.

Conclusion

A robust, fast and sensitive workflow for comprehensive drug residue analysis in water was established, combining online SPE, UHPLC and triple quadrupole MS with rapid polarity switching to meet stringent environmental monitoring requirements.

Reference

Levi M, Dufour C, Vecchioli I, Moreau S. Fast and sensitive analysis of drug residues in water using on-line SPE-UHPLC-MS/MS with ultra-fast polarity switching. ASMS 2015, Shimadzu Corporation, 2015.