Department of Pharmacy, Baotou Medical College, Inner Mongolia University of Science and Technology, Baotou 014060, China.
Chemical Pharmaceutical Research Center, Tasly Academy, Tasly Holding Group Co., Ltd., Tianjin 300410, China.
Molecules. 2022 Jun 27;27(13):4129. doi: 10.3390/molecules27134129.
A novel method of ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) was developed for the identification and quantification of four potential genotoxic impurities (PGIs) in the active pharmaceutical ingredients of TSD-1, a novel P2Y12 receptor antagonist. Four PGIs were named, 4-nitrobenzenesulfonic acid, methyl 4-nitrobenzenesulfonate, ethyl 4-nitrobenzenesulfonate, and isopropyl 4-nitrobenzenesulfonate. Following the International Conference of Harmonization (ICH) guidelines, this methodology is capable of quantifying four PGIs at 15.0 ppm in samples of 0.5 mg/mL concentration. This validated approach presented very low limits (0.1512−0.3897 ng/mL), excellent linearity (coefficients > 0.9900), and a satisfactory recovery range (94.9−115.5%). The method was sufficient in terms of sensitivity, linearity, precision, accuracy, selectivity, and robustness and, thus, has high practicality in the pharmaceutical quality control of TSD-1.
建立了一种超高效液相色谱串联质谱（UPLC-MS/MS）新方法，用于鉴定和定量TSD-1 新型 P2Y12 受体拮抗剂原料药中的 4 种潜在遗传毒性杂质（PGI）。这 4 种 PGI 分别命名为 4-硝基苯磺酸、甲基 4-硝基苯磺酸、乙基 4-硝基苯磺酸和异丙基 4-硝基苯磺酸。根据国际协调会议（ICH）指南，该方法能够在浓度为 0.5mg/mL 的样品中定量检测 15.0ppm 的 4 种 PGI。该方法经过验证，具有非常低的检测限（0.1512-0.3897ng/mL）、优异的线性（相关系数＞0.9900）和令人满意的回收率范围（94.9-115.5%）。该方法在灵敏度、线性、精密度、准确度、选择性和稳定性方面均表现出色，因此在 TSD-1 的药物质量控制方面具有很高的实用性。
