Study on related substances of TSD-1 — a novel P2Y12 receptor antagonist
10.16438/j.0513-4870.2022-0306
- VernacularTitle:新型P2Y12受体拮抗剂TSD-1的有关物质研究
- Author:
Tai-yu WANG
1
;
Jie YANG
2
;
Hai-long YANG
2
;
Guo-dong WU
3
;
Ming AN
3
;
Xue-yu XU
2
Author Information
1. Baotou Medical College, Baotou 014060, China; Tasly Institute, Tasly Holding Group, Tianjin 300410, China
2. Tasly Institute, Tasly Holding Group, Tianjin 300410, China
3. Baotou Medical College, Baotou 014060, China
- Publication Type:Research Article
- Keywords:
antiplatelet agent;
P2Y12 receptor antagonist;
related substance;
structure identification;
high performance liquid chromatography
- From:
Acta Pharmaceutica Sinica
2022;57(7):2177-2182
- CountryChina
- Language:Chinese
-
Abstract:
For quantitative analysis of related substances in TSD-1 active pharmaceutical ingredient, structures of prepared impurities were confirmed by NMR and UHPLC-MS, and a high performance liquid chromatographic method was established to determine the related substances in TSD-1. The analytical column was an Agilent ZORBAX Eclipe XDB-C8 (250 mm × 4.6 mm, 5 µm). The mobile phase A was 50 mmol·L-1 ammonium acetate solution (adjusted pH to 5.8 with acetic acid) and the mobile phase B was acetonitrile. The whole run was carried out by gradient elution at a flow rate of 1.0 mL·min-1. The detection wavelength was set at 240 nm and the column temperature was 30 ℃. The resolutions among peaks of TSD-1, impurity A, impurity B, TSD-D, and TSD-F were good. The calibration curves (n = 7) of TSD-1, impurity A, impurity B, TSD-D and TSD-F were linear in their respective weight ranges of 0.242-48.4 µg·mL-1 (r = 1.000 0), 0.244-9.75 µg·mL-1 (r = 0.999 9), 0.244-4.80 µg·mL-1 (r = 0.999 9), 0.254-1.02 µg·mL-1 (r = 0.999 9), and 0.247-0.987 µg·mL-1 (r = 0.999 9). The lower limits of quantitation were 0.244, 0.244, 0.254, and 0.247 µg·mL-1 for impurity A, impurity B, TSD-D, and TSD-F, respectively, and the average recovery of each impurity ranged from 99.08% to 103.00% with high accuracy. TSD-D and TSD-F were not detected in the three batches of TSD-1 active pharmaceutical ingredients, and impurity A and impurity B were not detected beyond the limit. The established HPLC method is simple, accurate, and suitable for determination of related substances of TSD-1, which can provide a valuable reference for the subsequent development of TSD-1.
