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. 2023 Apr;37(4):e5575.
doi: 10.1002/bmc.5575. Epub 2023 Jan 3.

Trace-level determination of potential genotoxic impurities in quetiapine fumarate using LC-MS

DasameswaraRao Kavitapu  1 , Ramana Reddy Gopireddy  1 , Arthanareeswari Maruthapillai  1 , Jayanti Naga Sri Rama Chandra Murty  2 , Naresh Kumar Katari  3
Affiliations

Trace-level determination of potential genotoxic impurities in quetiapine fumarate using LC-MS

DasameswaraRao Kavitapu et al. Biomed Chromatogr. 2023 Apr.

Abstract

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.

Keywords: 2-(2-aminophenylthio)benzoicacid hydrochloride; 2-(2-aminophenylthio)benzonitrile; 2-aminothiophenol; LC-MS; genotoxic impurities; quetiapine fumarate.

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References

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