Quantitative Determination of Four Potential Genotoxic Impurities in the Active Pharmaceutical Ingredients in TSD-1 Using UPLC-MS/MS

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 P2Y(12) 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.

Automated summary

A novel UPLC-MS/MS method was developed for the identification and quantification of four potential genotoxic impurities in the active pharmaceutical ingredients of a novel P2Y(12) receptor antagonist. This validated method showed low limits of detection, excellent linearity, and satisfactory recovery range, making it highly practical for pharmaceutical quality control of TSD-1.