Determination of Ticagrelor and its related impurities content from oral tablets as per proposed IP monograph UHPLC method

Significance of the Topic

The accurate quantification of pharmaceutical agents and their impurities is critical for ensuring drug safety and efficacy. Ticagrelor, a P2Y12 receptor antagonist used to prevent thrombotic events in acute coronary syndrome patients, requires stringent quality control. Implementing a robust UHPLC method according to the Indian Pharmacopeia (IP) monograph enables high-throughput analysis of tablet formulations, ensuring compliance with regulatory standards and protecting patient health.

Objectives and Study Overview

This study aims to validate an UHPLC assay and related substances test for Ticagrelor tablets based on the proposed IP monograph. Key goals include demonstrating that the Shimadzu Nexera XS system meets system suitability criteria, accurately quantifies drug content, and detects trace impurities within specified limits.

Methodology and Instrumentation

Chromatographic analyses were performed using the Shimadzu Nexera XS UHPLC system equipped with digital intelligence features for automated monitoring and diagnostics.

• Column: 150 mm×4.6 mm I.D., 1.8 µm, USP L1 packing.
• Column oven: 55 °C, Autosampler: 15 °C.
• Detector: UV at 242 nm.

For the assay:

• Mobile phase: Methanol/buffer (70:30), where buffer is 0.2 % w/v ammonium phosphate at pH 2.5.
• Solvent mixture: Acetonitrile/water (35:65).
• Standard solution: 0.5 mg/mL Ticagrelor in solvent.
• Sample preparation: Powder equivalent to 50 mg Ticagrelor sonicated in solvent and diluted to 100 mL.
• Flow rate: 1.2 mL/min, Injection: 5 µL, Run time: 10 min.

For related substances:

• Gradient between mobile phases A (buffer/water/acetonitrile, 10:890:100) and B (10:290:700).
• Flow rate: 1.0 mL/min, Run time: 35 min.
• Reference solutions containing low‐level Ticagrelor impurities prepared as per IP monograph.

Main Results and Discussion

Assay performance:

• Retention time of Ticagrelor: ~5.518 min.
• Peak tailing: 1.048 (≤1.5).
• %RSD (n=5) for retention time: 0.032 % and area: 0.135 % (≤2 %).
• Recovery for 60 mg and 90 mg tablets: 98.5–99.7 %, within 90–110 %.

Related substances performance:

• Retention time of Ticagrelor: ~12.926 min; impurity B: ~13.835 min with RRT 1.074.
• Resolution between Ticagrelor and impurity B: 6.336 (≥1.5).
• %RSD (n=5) for retention time: 0.050 % and area: 0.977 % (≤2 %).
• Signal-to-noise ratio for trace detection: 14.79 (≥10).
• Individual impurity levels ≤0.045 %, total ≤0.153 % (within 0.2 % and 0.5 % limits).

Benefits and Practical Applications

The validated UHPLC method using Shimadzu Nexera XS enables:

• Rapid, high-throughput analysis suitable for routine quality control.
• Reliable detection of low-level impurities, ensuring compliance with IP standards.
• Automated system suitability monitoring for consistent performance.

Future Trends and Applications

Advances in digital intelligence and IoT integration will further streamline UHPLC workflows. Emerging phases and detectors may enhance sensitivity for even lower impurity levels. The approach can be extended to other pharmaceutical compounds requiring stringent impurity profiling, harmonizing global pharmacopeial standards.

Conclusion

The Shimadzu Nexera XS UHPLC system successfully quantifies Ticagrelor content and related impurities in tablet formulations according to the proposed IP monograph. The method exhibits excellent precision, accuracy, and system suitability, making it well-suited for routine pharmaceutical quality control.