Improvement of pharmaceutical impurity analysis by reducing the effects of stray light and room temperature fluctuations on PDA detector

Importance of the Topic

Pharmaceutical impurity analysis is essential to ensure drug safety and efficacy. Accurate quantification of both high concentration active pharmaceutical ingredients and low level impurities is critical in drug development and quality control. Eliminating sources of error such as stray light and temperature‐induced baseline drift enhances analytical reliability.

Objectives and Study Overview

This study evaluates a new photodiode array detector, the SPD-M40, designed to reduce stray light and minimize baseline fluctuations caused by ambient temperature changes. The aim was to extend detector dynamic range, improve linearity up to at least 2.5 absorbance units, and enhance reproducibility in impurity assays of a model drug.

Methodology and Instrumentation

The analytical platform comprised a Shimadzu Nexera HPLC system equipped with the SPD-M40 PDA detector featuring a triple temperature control function for the flow cell, light source, and spectrometer. Two chromatographic methods were applied:

• Stray light evaluation: Shim-pack HRC-ODS column, 70 percent methanol mobile phase, 0.2 mL/min flow, detection at 273 nm, room temperature varied over 5 °C.
• Ketoprofen impurity assay: Shim-pack Velox C18 column, gradient of phosphate buffer (pH 2.6) and acetonitrile, 1.0 mL/min flow, detection at 256 nm, standard concentration range 0.5 to 800 mg/L.

Main Results and Discussion

Reducing stray light to one‐third of conventional PDA levels yielded linearity to 2.5 absorbance units with minimal deviation. Simulated stray light ratios up to 0.5 percent showed significant absorbance underestimation and nonlinearity beyond 2 AU for standard detectors. Temperature control experiments revealed that the SPD-M40 maintained baseline stability over 20–25 °C fluctuations, with peak area reproducibility below 1 percent relative standard deviation compared to nearly 2 percent for non‐controlled detectors. Ketoprofen assays demonstrated excellent linearity (R² ≥ 0.999) across three orders of magnitude. Six replicate analyses of a 700 mg/L standard showed impurity peak area RSD below 1 percent.

Benefits and Practical Applications

• Extended dynamic range enables simultaneous quantification of high concentration APIs and trace impurities without detector saturation.
• Stable baseline under variable laboratory conditions improves quantitative accuracy and reduces reruns.
• Enhanced reproducibility supports rigorous quality control in pharmaceutical manufacturing.

Future Trends and Opportunities

Further miniaturization of PDA detectors and integration with advanced data processing algorithms may enhance sensitivity and throughput. Coupling temperature‐controlled detectors with automated method development could accelerate impurity profiling for new drug candidates. Emerging spectroscopic materials and optical designs may further suppress stray light and push dynamic range limits.

Conclusion

The SPD-M40 PDA detector effectively minimizes stray light and ambient temperature effects, achieving a wide dynamic range, robust linearity, and high reproducibility in pharmaceutical impurity analysis. These improvements streamline quality control workflows and support compliance with regulatory standards.

References

1. Uchikata T, Akita S, Terada H, Watanabe M, Matsumoto K. Improvement of pharmaceutical impurity analysis by reducing the effects of stray light and room temperature fluctuations on PDA detector. Shimadzu Corporation, Kyoto, Japan.