Analysis of Paroxetine Hydrochloride

Significance of the topic

Paroxetine hydrochloride is a widely used antidepressant whose quality and purity must be rigorously monitored. Sensitive analytical methods are essential to detect trace-level impurities and ensure compliance with regulatory standards. Reversed-phase liquid chromatography on a C8 stationary phase offers robust separation performance for paroxetine and its degradation products.

Objectives and study overview

This application note demonstrates a validated reversed-phase HPLC method using a Shim-pack VP-C8 column for the simultaneous determination of paroxetine hydrochloride and two related impurities. The method aims to achieve baseline resolution, reliable system suitability, and reproducible quantitation in a single 75-minute run.

Methodology and instrumentation

Chromatographic conditions are as follows:

• Column: Shim-pack VP-C8, 250 mm × 4.6 mm I.D., 5 µm.
• Mobile phase A: TFA : THF : Water = 5 : 100 : 900 (v/v/v).
• Mobile phase B: TFA : THF : Acetonitrile = 5 : 100 : 900 (v/v/v).
• Gradient: 15 % B (0–5 min) → 25 % B (30 min) → 80 % B (50–60 min) → 15 % B (65–75 min).
• Flow rate: 1.0 mL/min; column temperature: 35 °C; injection volume: 20 µL; detection: UV at 295 nm.
• Sample preparation: Impurity standards and paroxetine hydrochloride each at 10 µg/mL in THF-water (1 : 9 v/v).

Main results and discussion

The system suitability solution produced three well-resolved peaks: Impurity I (defluparoxetine), Impurity II (N-methyl paroxetine), and paroxetine hydrochloride. Retention times were reproducible with theoretical plates exceeding method requirements and tailing factors within acceptable limits. The gradient program allowed clear separation without coelution, even at low impurity levels.

Benefits and practical applications

The described method delivers high specificity, sensitivity, and robustness, making it suitable for routine quality control of paroxetine formulations. Its clear baseline separation supports reliable quantitation of trace impurities, ensuring patient safety and meeting pharmacopeial guidelines.

Future trends and potential applications

Advances in column chemistries and faster gradient systems may shorten analysis time while maintaining separation quality. Coupling with mass spectrometry could enhance impurity identification and quantitation at trace levels. Automation and online sample prep will further increase laboratory throughput.

Conclusion

This reversed-phase HPLC method on a Shim-pack VP-C8 column provides a robust, reproducible, and regulatory-compliant approach for the analysis of paroxetine hydrochloride and its related impurities. It supports stringent quality control in pharmaceutical development and manufacturing.

Reference

Shimadzu Corporation. Application Note ERAS-1000-0075, First Edition: Mar. 2023.