Kavitapu DasameswaraRao, Gopireddy Ramana Reddy, Maruthapillai Arthanareeswari, Murty Jayanti Naga Sri Rama Chandra, Katari Naresh Kumar
Department of Chemistry, SRM Institute of Science and Technology, Kattankulathur, India.
Analytical Discovery Chemistry, Aragen Life Sciences Pvt. Ltd., IDA Nacharam, Hyderabad, India.
Biomed Chromatogr. 2023 Apr;37(4):e5575. doi: 10.1002/bmc.5575. Epub 2023 Jan 3.
A novel LC-MS method was developed and validated to determine three potential genotoxic impurities, namely 2-(2-aminophenylthio)benzoic acid hydrochloride, 2-aminothiophenol, and 2-(2-aminophenylthio)benzonitrile, at trace level (~1.6 ppm) in quetiapine fumarate drug substance, an antipsychotic drug. These impurities are potentially genotoxic and therefore should be controlled at or below specific acceptance limits. An InertSustain AQ-C18 column (250 × 4.6 mm, 5 μm) in reversed-phase mode with the column temperature at 45°C was used. The mobile phase was 0.1% trifluoroacetic acid in water and acetonitrile with gradient elution mode, and the run time was 45 min. The flow rate was 0.8 ml/min. A mass spectrometer was used to quantify the amount of impurities using electrospray ionization mode at specific m/z 245.9, 126.0, and 226.9 for 2-(2-aminophenylthio)benzoic acid hydrochloride, 2-aminothiophenol, and 2-(2-aminophenylthio) benzonitrile, respectively. The method was found to be sensitive and possessed excellent linearity in the concentration ranges from the limit of quantification to 150% of the permitted level (0.47-2.36 μg/ml) with correlation coefficients above 0.999. The results showed that the method was specific, precise, linear, and accurate for the estimation of these three impurities in quetiapine fumarate.
开发并验证了一种新型液相色谱 - 质谱（LC-MS）方法，用于测定抗精神病药物富马酸喹硫平原料药中痕量水平（约1.6 ppm）的三种潜在遗传毒性杂质，即盐酸2-(2-氨基苯硫基)苯甲酸、2-氨基苯硫酚和2-(2-氨基苯硫基)苯甲腈。这些杂质具有潜在遗传毒性，因此应控制在特定可接受限度或以下。采用InertSustain AQ-C18色谱柱（250×4.6 mm，5μm），反相模式，柱温45°C。流动相为含0.1%三氟乙酸的水和乙腈，采用梯度洗脱模式，运行时间为45分钟。流速为0.8 ml/min。使用质谱仪，采用电喷雾电离模式，分别在特定的m/z 245.9、126.0和226.9下对盐酸2-(2-氨基苯硫基)苯甲酸、2-氨基苯硫酚和2-(2-氨基苯硫基)苯甲腈的杂质含量进行定量。该方法在定量限至允许水平的150%（0.47 - 2.36μg/ml）浓度范围内具有良好的灵敏度和线性，相关系数高于0.999。结果表明，该方法对于富马酸喹硫平中这三种杂质的测定具有特异性、精密度、线性和准确性。
