Abstract
A liquid chromatography with single quadrupole mass detection method was developed for the determination of potential genotoxic impurities (PGIs) in the Iomeprol active pharmaceutical ingredient. Chromatographic separation was achieved on an Agilent Eclipse plus C8 column (100 mm x 2.1 mm x 1.8 μm) with 0.1% formic acid in water as mobile phase A and acetonitrile as mobile phase B in gradient elution mode at a 0.1 mL/min. Executed validation summary demonstrated that the mass detection method had highly sensitive and selective. A linear calibration curve (correlation coefficient, r> 0.999) was attained at the concentration range of 0.1-125 ppm for three PGI’s. The Limit of Detection of Imp-A, Imp-B and Imp-C in drug substance of Iomeprol is 0.05 ppm. The accuracy was confirmed by calculated recoveries (98.4-101.5%). The precision was tested at three levels: injection repeatability, analysis repeatability and intermediate precision. The calculated relative standard deviations were within the specification. The developed method was able to quantitate all three PGI’s at a concentration level of 1 µg/mL.
Highlights
These Genotoxic impurities have ability to react with Deoxyribonucleic acid (DNA), causing oncological risk in patients even at lower level (1 ppm below)
The impurities which have structural alerts and may cause the cancer in patients are called as potential Genotoxic impurities (PGIs) [6]
Iomeprol is classified as a water soluble neurotrophic low osmolar X-ray contrast medium
Summary
These Genotoxic impurities have ability to react with Deoxyribonucleic acid (DNA), causing oncological risk in patients even at lower level (1 ppm below) These impurities are produced during the manufacturing of drug substance and other possible source is synthesis of raw materials, intermediates, by-products and degradation of drug substances in storage. As per the literature still ICMS’s are tested in plasma and in water [13,14,15,16,17] in continuation of our work on the development and sensitive LCMS method was developed for the determination of potential Genotoxic impurities materials: Imp-A, Imp-B and Imp-C in Iomeprol drug substance and the validation of this method was performed according to the ICH guidelines [18]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
