Highly Sensitive Detection of Pharmaceuticals and Personal Care Products (PPCPs) in Water Using an Agilent 6495 Triple Quadrupole Mass Spectrometer

Significance of the topic

Pharmaceuticals and personal care products (PPCPs) have been detected at part-per-trillion levels in surface and drinking water worldwide. Their persistence and potential ecological and human health impacts drive the need for highly sensitive, accurate, and efficient analytical methods. Regulatory agencies such as the U.S. EPA and the European Water Framework Directive are proposing limits for trace contaminants, making rapid, routine monitoring critical in water quality assessment.

Objectives and Study Overview

This study aimed to develop and demonstrate two high-sensitivity liquid chromatography–tandem mass spectrometry (LC-MS/MS) methods for the direct detection and quantitation of a broad panel of PPCPs at ppt levels. One method operates in positive ion mode for 118 target compounds (316 dynamic MRM transitions), and the other in negative ion mode for 22 compounds (62 transitions). The goal was to eliminate solid-phase extraction, streamline workflow, and maintain precise quantitation down to 10 ppt.

Methodology

Water samples were filtered, spiked with isotopically labeled internal standards (250 ppt), and directly injected (40 µL) onto the LC system. Dynamic multiple reaction monitoring (dMRM) was used to sequence transitions for each analyte. Calibration curves were prepared in ultrapure water at seven levels (10–1 000 ppt), fitted with quadratic regressions (1/x weighting), achieving correlation coefficients (R²) above 0.99 for nearly all compounds. Precision and accuracy were evaluated by replicate injections and recovery checks across low and high concentration levels. Real-world samples included local tap water, a remote source, and an urban surface water, each analyzed in duplicate.

Instrumentation

• Agilent 6495 Triple Quadrupole mass spectrometer with Jet Stream electrospray ionization
• Agilent 1290 Infinity UHPLC system (binary pump, autosampler with cooling, thermostatted column compartment)
• ZORBAX Eclipse Plus C18 column (2.1 × 100 mm, 1.8 µm) at 40 °C
• Agilent MassHunter Acquisition, Qualitative, and Quantitative Analysis B.07 software

Main results and discussion

The optimized ion optics and curved collision cell of the 6495 TQ MS provided significant signal enhancement, enabling limits of detection and quantitation well below 10 ppt without sample enrichment. Calibration for key analytes such as metformin (positive mode) and ibuprofen (negative mode) exhibited excellent linearity (R² > 0.999). Most compounds met precision (RSD < 15 %) and accuracy (80–120 %) criteria. A small subset of hydrophobic analytes showed low-level bias due to adsorption in autosampler vials. In real samples, positive mode analysis identified multiple PPCPs in tap and source waters (e.g., gabapentin, metformin, DEET, caffeine). Negative mode screening of urban surface water revealed nonpolar analytes such as ibuprofen, naproxen, and triclosan above 10 ppt. A suite of PDF report templates in MassHunter Quantitative Analysis facilitated automated result generation and flexible layout design.

Benefits and practical applications

The methods eliminate laborious solid-phase extraction, reducing solvent use and sample handling. Direct injection of small volumes accelerates throughput while maintaining ppt-level sensitivity. This streamlined workflow supports routine monitoring in environmental, regulatory, and water utility laboratories. The dynamic MRM approach allows broad multiresidue screening with reliable quantitation.

Future trends and applications

Further expansion of compound libraries, adaptation to other matrices (e.g., wastewater, biosolids), and coupling with automated sample preparation will enhance monitoring capabilities. Integration with high-resolution mass spectrometry and real-time data processing could enable rapid pollutant tracking and risk assessment in diverse water systems.

Conclusion

The Agilent 6495 Triple Quadrupole LC/MS workflow delivers robust, high-throughput detection of over 140 PPCPs at part-per-trillion levels via direct injection. The combined sensitivity, accuracy, and reporting flexibility make it a powerful tool for trace contaminant monitoring in drinking and environmental waters.

References

1. Boyd GR, et al. Pharmaceuticals and Personal Care Products in Surface and Treated Waters of Louisiana, USA and Ontario, Canada. Science of The Total Environment 311(1–3):135–149, 2003.
2. Snyder SA, et al. Pharmaceuticals, Personal Care Products, and Endocrine Disruptors in Water: Implications for the Water Industry. Environmental Engineering Science 20(5):449–469, 2003.
3. USEPA Method 1694: Pharmaceuticals and Personal Care Products in Water, Soil, Sediment, and Biosolids by HPLC/MS/MS (EPA-821-R-08-002, 2007).
4. European Water Framework Directive 2000/60/EC and Groundwater Directive 2006/118/EC.
5. Ferra I, Thurman EM, Zweigenbaum J. Ultrasensitive EPA Method 1694 with Agilent 6460 LC/MS/MS with Jet Stream Technology for Pharmaceutical and Personal Care Products in Water. Agilent Technologies Application Note 5990-4605EN.
6. Cullum N. Optimizing Detection of Steroids in Wastewater Using the Agilent 6490 Triple Quadrupole LC/MS System with iFunnel Technology. Agilent Technologies Application Note 5990-9978EN.
7. Yang DD, et al. Multi-Residue Pesticide Screening and Quantitation in Difficult Food Matrixes Using the Agilent 6495 Triple Quadrupole Mass Spectrometer. Agilent Technologies Application Note 5991-4687EN.