HPLC method for simultaneous analysis of ticagrelor and its organic impurities and identification of two major photodegradation products

- Validated method for ticagrelor and its synthesis impurities simultaneous analysis was developed.
- Two major photodegradation products were chemically elucidated.
- The photodegradation pathways were proposed.

A simple, fast and sensitive analytical method by high-performance liquid chromatography (HPLC) was developed and validated for the simultaneous determination of ticagrelor and two synthesis impurities. The HPLC method was established using an Agilent 1200 Series equipment coupled to photodiode array detector (PDA) at 270 nm with a Zorbax Plus C8 column (150 × 4.6 mm, 5.0 μm), injection volume of 20 μL, and a constant temperature of 25 °C. The mobile phase consisted of acetonitrile: ammonium acetate 50 mM (57:43, v/v) and pH adjusted to 8.2 with ammonium hydroxide 6 M, at a flow rate of 0.7 mL/min. No interference peaks from excipients and diluent system indicated the specificity of the method. The calibration curves showed determination coefficients (r2) > 0.99, calculated by linear regression. The limit of quantitation (LOQ) for impurities 1 and 2 were 2.0 and 0.2 μg/mL, respectively. Intra and interday relative standard deviations (RSDs) were < 2% for ticagrelor and < 6% for the impurities, proving the precision of the method. Besides, two mayor degradation products formed when sample solutions of ticagrelor were exposed to UVC radiation were elucidated and the mechanisms involved in the photolytic degradation of ticagrelor were proposed.

76