Cupric chloride assay by ion chromatography

Significance of the topic

Copper chloride is widely used for nutritional supplementation in total parenteral nutrition and pharmaceutical applications. The existing USP monograph relies on a wet chemical titration that is laborious and involves hazardous reagents. An automated ion chromatography approach can improve safety, speed, and reproducibility, aligning with modern monograph modernization initiatives.

Goals and study overview

This work develops and validates an ion chromatography assay for cupric chloride based on direct copper determination. The method uses a Dionex IonPac CS5A column, pyridine dicarboxylic acid eluent, and post column derivatization with PAR reagent. Validation follows USP chapter 1225 guidelines and aims to demonstrate sensitivity, precision, and robustness suitable for replacing the USP titration procedure.

Instrumentation

• Thermo Scientific Dionex ICS-5000+ reagent free ion chromatography system or equivalent ICS-6000
• DP dual pump with degas, DC detector compartment with dual temperature zones
• Thermo Scientific Dionex AS-AP autosampler with tray temperature control and 6.5 microliter loop
• Dionex IonPac CG5A guard column and CS5A analytical column 2 by 250 millimeter
• Post column reaction coil 125 microliter and PAR reagent delivery
• UltiMate 3000 DAD detector set at 530 nanometer

Methodology and instrumentation

Isocratic elution with 2 millimolar PDCA at 0.3 milliliter per minute and column temperature 30 degrees Celsius. Post column reaction with PAR at 0.15 milliliter per minute in a 125 microliter coil yields a colored complex detected at 530 nanometer. Calibration standards spanning 0.05 to 10 milligrams per liter copper were prepared in 2 millimolar nitric acid. System was conditioned to minimize baseline noise and pressure fluctuations.

Main results and discussion

• Separation of copper from iron and nickel achieved within 11 minutes with baseline resolution
• Linearity over 0.05 to 10 mg/L with r2 of 0.9999
• Limit of detection 0.015 mg/L and limit of quantitation 0.05 mg/L (S/N 3 and 10)
• Accuracy recoveries between 98 and 103 percent at three spike levels
• Precision RSD of retention time below 0.2 percent and peak area below 3.2 percent
• Robustness demonstrated under +/-10 percent variation in flow rate, eluent concentration, and temperature with minimal effect on retention time, asymmetry, and resolution
• Analysis of a 5 mg/L test solution gave 100.23 percent label claim, within USP limits

Benefits and practical applications

• Fully automated workflow reduces manual handling and hazardous reagent use
• High sensitivity and selectivity for trace copper analysis in pharmaceutical substances
• Rapid turnaround supports high throughput quality control environments
• Method is easily transfered between labs using common IC instrumentation

Future trends and opportunities

Extension of this IC approach to other transition and lanthanide metals may streamline multi element assays. Coupling with mass spectrometry could further enhance sensitivity and speciation analysis. Integration with fully automated sample preparation and data processing will advance pharmaceutical quality control and environmental monitoring applications.

Conclusion

The ion chromatography assay for cupric chloride offers a robust, accurate, and efficient alternative to USP titration, satisfying validation requirements and modernizing the monograph. It combines rapid separation, sensitive detection, and automation for reliable copper quantification.

References

• Shike M Copper in parenteral nutrition Gastroenterology 2009 137 S13 S17
• Cupric Chloride US Pharmacopeial Convention USP42 NF37 p1167
• USP Seeks Submission of Proposals for Monograph Modernization US Pharmacopeia website accessed 2019
• Validation of Compendial Methods General Chapter 1225 US Pharmacopeia USP42 NF37 p8046
• Physical Tests 621 Chromatography US Pharmacopeia USP42 NF37 p6781