X-Ray Fluorescence Analysis of Crude Drugs

Significance of the topic

Energy-dispersive X-ray fluorescence (EDXRF) offers a rapid, non-destructive approach to assessing inorganic composition in crude drugs and botanical materials. Determining mineral content and hazardous heavy metals is essential for product safety, regulatory compliance (for example Japanese Pharmacopoeia limits), and quality control across cultivation and processing variations. EDXRF can reduce sample-preparation workload and throughput time compared with wet-chemistry and plasma-based techniques, making it attractive for routine screening in pharmaceutical and natural-product laboratories.

Objectives and overview of the study

This work demonstrates the capabilities of the ALTRACE EDXRF spectrometer for: (1) targeted quantitative screening of hazardous heavy metals (Pb, As, Cd, Hg) using calibration curves and (2) comprehensive qualitative–quantitative multi-element profiling from Na to U using the Fundamental Parameter (FP) method. Five commercially available crude drugs (cinnamon bark, citrus unshiu peel, coptis rhizome, glycyrrhiza, pueraria root) were analyzed to assess detection limits, repeatability, and applicability relative to the Japanese Pharmacopoeia (JP) requirements.

Methodology

• Sample preparation: Minimal preparation — samples crushed and placed in a sample cell sealed with a 5 μm polypropylene film and lightly compressed.
• Quantification approaches: Two workflows were used: (a) calibration curve method for Pb, As, Cd, Hg with aqueous atomic absorption (AA) standards at multiple concentrations; (b) FP method for multi-element qualitative and quantitative analysis without external standards.
• Calibration & corrections: Calibration used AA standard solutions at 0–40 ppm (Hg 0–20 ppm). Corrections included internal standard normalization using scattered X-rays to compensate matrix effects and a coexisting-element correction (dj method) to address As/Pb spectral overlap.
• Analysis parameters: Measurements used an ALTRACE EDXRF with silicon drift detector (SDD) and Rh X-ray tube. Tube voltages ranged from 15 to 65 kV depending on channels. Integration times of 60 s (FP multi-element) to 300 s (heavy metals) were applied; atmospheres were air or vacuum as appropriate.

Instrumentation

• Instrument: ALTRACE energy-dispersive X-ray fluorescence (EDXRF) spectrometer (Shimadzu).
• X-ray tube: Rhodium (Rh) target; selectable tube voltages (15–65 kV) and automated tube current control.
• Detector: Silicon drift detector (SDD).
• Measurement modes: Calibration curve quantification and FP (fundamental parameter) quantification.
• Sample holder: Polypropylene film-lined cell (5 μm film) used for non-destructive placement of powders/solids.

Main results and discussion

• Sensitivity and limits: Lower limits of quantitation (LLOQ) were approximately 0.2 ppm for As, Hg, and Pb, and approximately 0.5 ppm for Cd (integration time 300 s). These LLOQs are below JP control thresholds (heavy metals: typically 10 ppm; arsenic: 5 ppm), indicating suitability for regulatory screening.
• Calibration performance: Calibration curves for Pb, As, Cd and Hg showed excellent linearity (correlation coefficients ≈0.998–0.999) and accuracies within about 0.5 ppm or better. As calibration required spectral-overlap correction with Pb.
• Quantitative screening results (calibration-curve method): Most samples contained heavy metals well below JP limits. Notable values: coptis rhizome showed Pb ∼1.35 ppm, As ∼0.24 ppm, Cd ∼0.78 ppm; cinnamon bark Pb ∼0.84 ppm; pueraria root Pb ∼0.28 ppm. Many results were below respective LLOQs and reported as < LLOQ.
• Repeatability: Ten consecutive analyses of coptis rhizome gave Pb mean ≈1.37 ppm with coefficient of variation (CV) 1.5%, indicating high precision. As and Cd near LLOQ showed CVs around 7–8%.
• FP multi-element profiling: FP quantification detected and quantified major mineral components (Ca, K, S, P, Mg) and trace elements (Fe, Mn, Zn, Cu, Sr, Rb, Ba, Pb) across the five samples. Organic matrix was modeled as cellulose (C6H10O5) for FP computations and accounted for ~98% of mass in the calculation, enabling reasonable matrix correction for inorganic determinations.
• Spectral issues and limitations: Overlap of As Kα with Pb Lα required computational correction; light elements below Na are not measurable by EDXRF; organic elements (C, H, O) are inferred rather than directly measured. For ultra-trace (<0.1 ppm) analysis, plasma-based techniques (ICP-MS) remain superior.

Benefits and practical applications

• Non-destructive, minimal sample preparation — samples remain available for confirmatory methods.
• Rapid throughput — suitable for routine screening and high sample volumes in QC labs.
• Multi-element capability — FP enables broad elemental surveys (Na–U) to profile mineral content and contaminants simultaneously.
• Regulatory screening fit — demonstrated LLOQs and precision are adequate for initial compliance checks versus JP heavy-metal and arsenic thresholds.
• Lower operational complexity and infrastructure needs compared with AAS, ICP-AES, or ICP-MS, reducing cost and training barriers for screening workflows.

Future trends and potential applications

• Integration with chemometric and machine-learning tools to accelerate classification of botanical origins, detect adulteration, and predict element sources from spectral fingerprints.
• Deployment of benchtop and portable EDXRF for at-line screening at collection/processing sites, enabling earlier detection of contamination.
• Improved FP algorithms and spectral-deconvolution techniques to further reduce overlap errors (e.g., As/Pb) and increase accuracy at lower concentrations.
• Hybrid workflows: use EDXRF as a front-line screening tool with targeted confirmatory analysis (ICP-MS/AAS) for samples near regulatory limits or requiring speciation.
• Broader regulatory acceptance as performance data accumulate and standardized protocols emerge for botanical materials.

Conclusion

ALTRACE EDXRF provides an efficient, reliable screening method for heavy metals and mineral components in crude drugs. The system demonstrated adequate sensitivity, linearity, and repeatability for regulatory screening relative to the Japanese Pharmacopoeia limits, while offering practical advantages in speed, sample handling, and non-destructiveness. EDXRF is well suited for routine quality control and preliminary compliance assessment; where ultra-trace quantitation or speciation is required, complementary wet-chemical or plasma-based methods should be used for confirmation.

References

1. Tamura Y., Moriya H. X-Ray Fluorescence Analysis of Crude Drugs. Shimadzu Application Note (ALTRACE EDXRF). First Edition: Oct. 2026.
2. Japanese Pharmacopoeia, Eighteenth Edition. Standards for heavy metals and arsenic limits referenced in the study.