Quantitative Determination of Four Potential Genotoxic Impurities in the Active Pharmaceutical Ingredients in TSD-1
Taiyu Wang1,2, Hailong Yang2, Jie Yang2
1Department of Pharmacy, Baotou Medical College, Inner Mongolia University of Science and Technology, Baotou 014060, China.
Abstract:
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.
Insights
A new UPLC-MS/MS method accurately quantifies four potential genotoxic impurities in TSD-1, a P2Y12 receptor antagonist. This validated approach ensures pharmaceutical quality control for TSD-1 manufacturing.
Area of Science:
- Analytical Chemistry
- Pharmaceutical Analysis
Background:
- Potential genotoxic impurities (PGIs) require sensitive detection in active pharmaceutical ingredients.
- TSD-1 is a novel P2Y12 receptor antagonist with specific PGIs needing control.
Purpose of the Study:
- To develop and validate a novel ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method.
- To identify and quantify four specific PGIs in TSD-1 active pharmaceutical ingredients.
Main Methods:
- Ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) was employed.
- Method validation was performed according to International Conference of Harmonization (ICH) guidelines.
Main Results:
- The method successfully identified and quantified four PGIs: 4-nitrobenzenesulfonic acid, methyl 4-nitrobenzenesulfonate, ethyl 4-nitrobenzenesulfonate, and isopropyl 4-nitrobenzenesulfonate.
- Quantification achieved 15.0 ppm in 0.5 mg/mL samples with low limits (0.1512–0.3897 ng/mL) and excellent linearity (R² > 0.9900).
- Satisfactory recovery (94.9–115.5%) and demonstrated robustness confirmed method suitability.
Conclusions:
- The validated UPLC-MS/MS method is sensitive, accurate, and robust for PGI quantification.
- This method is highly practical for pharmaceutical quality control of TSD-1.
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