Combined Contaminant and Multi-Residue Testing by LC/MS/MS for the Quality Control of Herbal Drugs used in Traditional Chinese Medicine (TCM)

Importance of the Topic

The safety of traditional Chinese medicines relies on comprehensive monitoring of chemical contaminants. Large-scale cultivation often involves agrochemicals, increasing the risk of pesticide residues, mycotoxins and pyrrolizidine alkaloids in finished herbal products. A streamlined multi-residue LC/MS/MS approach is essential to ensure product quality and protect consumer health.

Study Objectives and Overview

This work presents the development and application of a unified ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) method. It is designed to screen and estimate concentrations of over 300 pesticides, mycotoxins and pyrrolizidine alkaloids in ten widely used TCM herbal drugs. The method aims for rapid throughput, high sensitivity and compliance with regulatory guidelines.

Methodology and Instrumentation

• Sample Preparation
  • 2 g of pulverized herbal material extracted via a modified QuEChERS protocol.
  • Enhanced Matrix Removal (EMR) cleanup with dispersive SPE and MgSO₄ to reduce matrix effects.
  • Filtration through 0.45 µm PTFE membrane before analysis.
• Chromatography
  • Column: Agilent Poroshell 120 EC-C18, 2.1 × 100 mm, 2.7 µm at 20 °C.
  • Mobile Phase: 5 mM ammonium formate/0.1% formic acid water and methanol gradient.
  • Flow Rate: 0.6 mL/min; total run time 20 min with rapid re-equilibration.
• Mass Spectrometry
  • Agilent 6495 Triple Quadrupole with Jet Stream ESI.
  • Dynamic multiple reaction monitoring (MRM) with fast polarity switching.
• Calibration: Standard addition or matrix-matched calibrations covering 0.1–100 µg/kg in solvent and 0.5–100 µg/kg in matrix.

Major Findings and Discussion

• Recoveries: 82% of analytes achieved >70% recovery, meeting SANTE guidelines.
• Contaminant Profiles: Seven pesticides detected across samples at 0.8–185.7 µg/kg; no mycotoxins or pyrrolizidine alkaloids found.
• Regulatory Exceedances: Four pesticides surpassed EU maximum residue limits, notably carbendazim in Mori folium (185.7 µg/kg) and MCPA in Herba epimedii (116 µg/kg).
• Interpretation: Carbendazim may originate from parent fungicides or degradation of benomyl/thiophanate-methyl. Detection of banned DNOC underscores the need for rigorous surveillance.

Benefits and Practical Applications

This validated workflow enables:

• Simultaneous multi-class contaminant screening in a single 20 min run.
• Robust matrix cleanup for diverse herbal matrices.
• Enhanced sensitivity and quantitative confidence for quality control laboratories.
• Compliant results aligned with international regulatory standards.

Future Trends and Opportunities

Potential developments include:

• Expanding to non-target screening of emerging contaminants using high-resolution MS.
• Automating sample preparation and data analysis to improve throughput.
• Integrating retrospective data mining for legacy sample re-analysis.
• Applying similar workflows to other natural products such as dietary supplements and nutraceuticals.

Conclusion

The combined UHPLC-MS/MS method with QuEChERS and EMR cleanup offers a powerful tool for routine quality control of TCM herbal drugs. It delivers high recovery, broad contaminant coverage and rapid analysis, helping to close safety gaps and support regulatory compliance.

Reference

• Ferrer Amate C et al. Anal Bioanal Chem 2010;397:93–107.
• Bolechová M et al. Food Chem 2015;170:265–270.
• Sack C et al. J Agric Food Chem 2015;63:9657–9665.
• EU Pesticides Database (Regulation EC 396/2005).
• SANTE/11945/2015 Guidelines for Recoveries and Method Validation.