Entire Workflow from Dissolution Sampling, LIMS, HPLC Measurement to Result

Significance of the Topic

Pharmaceutical dissolution testing is a fundamental quality control and development tool to ensure uniformity, assay accuracy, and controlled drug release from solid dosage forms. When products contain multiple active pharmaceutical ingredients (APIs) across a wide concentration range, conventional UV spectroscopy may face selectivity and dynamic range limitations. Implementing high-performance liquid chromatography (HPLC) equipped with a high-dynamic-range (HDR) detector provides robust separation and quantification of both high- and low-abundance APIs in a single run while maintaining regulatory compliance and operational efficiency.

Objectives and Overview of the Study

This application note demonstrates a fully integrated workflow from dissolution sampling to final result analysis using an Agilent 1290 Infinity III LC system with HDR detection. Four APIs—vitamin C, paracetamol, caffeine, and chlorphenamine—present in a capsule formulation with widely varying concentrations were quantified in a single HPLC run. Barcoded sample vials, a laboratory information management system (LIMS), and an onboard sample ID reader streamline sample tracking and reduce the risk of mix-ups.

Methodology and Instrumentation

The following equipment and materials were used:

• Agilent 708-DS Dissolution Apparatus with 850-DS autosampler
• Agilent 1290 Infinity III high-speed pump, hybrid multisampler with InfinityLab sample ID reader, multicolumn thermostat, and dual diode array detectors with Max-Light cartridges
• Agilent ZORBAX Eclipse Plus C18, RRHD, 2.1 × 100 mm, 1.8 µm column
• Agilent OpenLab CDS software with Sample Scheduler
• 0.1 N HCl dissolution medium, 900 mL per vessel, 37 °C, 75 rpm stirring

Dissolution samples (1 mL) were withdrawn at 10, 20, 40, 60, and 75 minutes, filtered, and dispensed into barcoded 2 mL vials. Sample metadata from the LIMS were imported into the Sample Scheduler, and vial barcodes were scanned by the multisampler reader to confirm sequence alignment before analysis.

Main Results and Discussion

The integrated workflow allowed seamless transfer of sample IDs from LIMS to the HPLC sequence, with real-time progress monitoring in Sample Scheduler. The HDR detection combined signals from short and long path-length DAD cells, capturing high-abundance APIs (vitamin C, paracetamol) and low-abundance chlorphenamine without detector saturation. All four APIs were baseline-resolved, and dissolution profiles achieved complete release (100%) over the 75-minute timeframe.

Benefits and Practical Applications of the Method

• Simultaneous quantification of multiple APIs across a broad concentration range in one HPLC run
• Reduced analysis time and cost by avoiding separate assays for high- and low-level compounds
• Minimized sample mix-up risk through barcode tracking and LIMS integration
• Improved ease-of-use and data integrity via Agilent Sample Scheduler

Future Trends and Potential Applications

Automation and digital integration in pharmaceutical analytics are expected to advance further, with enhanced LIMS connectivity, real-time data reporting, and expanded use of HDR detectors for complex drug formulations. Machine learning-driven method optimization and cloud-based sample management may provide additional efficiency gains and regulatory transparency.

Conclusion

The described workflow demonstrates a robust, time-saving approach for dissolution testing of multi-API capsules. Combining HDR HPLC detection with barcode-enabled sample tracking and LIMS integration delivers high data quality, operational efficiency, and scalability for pharmaceutical quality control laboratories.

References

1. Confirmation of Sample Position – Using the Agilent 1290 Infinity III Multisampler with Agilent InfinityLab Sample ID Reader – Part 1 of 2. Agilent Technologies technical overview, publication number 5994-7568EN, 2024.
2. Sample Position Identification and Measurement Confirmation – Using the Agilent 1290 Infinity III Multisampler with Agilent InfinityLab Sample ID Reader – Part 2 of 2. Agilent Technologies technical overview, publication number 5994-7569EN, 2024.
3. Agilent Advanced Sample Linking – A Complete Workflow from Any Laboratory Information Management System to the Vial and Analytical Results. Agilent Technologies white paper, publication number 5994-7570EN, 2024.
4. Schneider S. Impurity Testing of Fixed-Dose Combination Drugs Using the Agilent 1290 Infinity II HDR-DAD Impurity Analyzer Solution. Agilent Technologies application note, publication number 5991-5743EN, 2015.