Method Verification of the United States Pharmacopeia Monograph with the Agilent Cary 60 UV-Vis

Significance of the topic

Pharmaceutical compendial methods require rigorous verification to ensure drug safety, efficacy, and regulatory compliance.
UV-Vis spectroscopy is commonly specified in pharmacopeial monographs for quantifying impurities, such as iron in magnesium sulfate, making reliable instrumentation essential for quality control.

Objectives and study overview

This work demonstrates the verification of the USP monograph for iron impurities in magnesium sulfate using an Agilent Cary 60 UV-Vis spectrophotometer equipped with an 18-cell multicell changer and controlled by Cary WinUV software.
The study encompassed accuracy, precision, specificity, and quantitation limit tests as described in USP <857>, and applied the verified method to two real samples against the USP limit of 0.5 µg/g.

Methodology and instrumentation

Reagents and sample preparation followed USP guidelines: dilute HCl as solvent, ammonium acetate buffer, ascorbic acid reductant, and a triazine-based color reagent.
Three matrix-matched iron standards (0.04, 0.10, 0.20 mg/L) and blank were prepared; sample solutions were made by dissolving 10 g magnesium sulfate in dilute HCl.
Measurements were performed at 594 nm, 1.5 nm spectral bandwidth, 0.5 s averaging time, and 1 cm pathlength cells using the Cary 60 UV-Vis with an 18-cell changer and Cary WinUV Concentration application.

Main results and discussion

Recovery (accuracy) ranged from 94.6% to 102.0%, within the USP acceptance of 80–120%.
Precision (repeatability) showed an RSD of 1.8%, well below the 15–20% limit.
Specificity was confirmed by spectral scans showing no interference at 594 nm in the blank.
The quantitation limit was estimated at 0.00231 mg/L (10× blank standard deviation), meeting signal-to-noise >10 and monograph requirements.
Measured iron contents in two samples were 0.31 and 0.25 µg/g, below the USP maximum of 0.5 µg/g.

Benefits and practical applications

The automated multicell changer simplifies replicate measurements and reduces operator workload, enhancing throughput.
The robust xenon lamp offers a 10-year warranty, lowering downtime and revalidation costs.
The verified method is ideal for routine pharmaceutical QA/QC and research laboratories seeking compliance with USP compendial procedures.

Future trends and opportunities

Integration with electronic record systems for 21 CFR Part 11 and EU Annex 11 compliance.
Extension of automated UV-Vis workflows to additional pharmacopeial assays.
Adoption of eco-certified instrumentation to support greener laboratory practices.
Further automation and software enhancements to increase throughput and data integrity.

Conclusion

The Agilent Cary 60 UV-Vis with an 18-cell changer successfully verified the USP procedure for iron in magnesium sulfate, meeting all validation criteria.
This configuration provides a reliable, efficient solution for pharmaceutical quality control and R&D applications.

References

• United States Pharmacopeia. General Chapter 1226 Verification of Compendial Procedures. USP-NF. Rockville, MD: United States Pharmacopeia, 2024.
• United States Pharmacopeia. General Chapter 857 Ultraviolet-Visible Spectroscopy. USP-NF. Rockville, MD: United States Pharmacopeia, 2022.
• Agilent Technologies. Spectroscopy Solutions for Pharmaceuticals: Confidence in Compliance to USP 857 Using the Agilent Cary 60 UV-Vis Spectrophotometer. White Paper 5991-7269EN, 2016.
• United States Pharmacopeia. Magnesium Sulfate Monograph. USP-NF. Rockville, MD: United States Pharmacopeia, 2024.
• Agilent Technologies. Improved Lab Efficiency with the Agilent 18-Cell Changer Accessory. Technical Overview 5994-7250EN, 2024.