Abstract:
:Impurities in drug substances and drug products generally do not have beneficial effects and may impose a risk without associated benefit. Levofloxacin n-oxide is an impurity isolated from levofloxacin. However there is insufficient toxic information about levofloxacin n-oxide. This study investigates the genotoxicity of this impurity by in silico and in vitro methods. We used Derek, a commercial structure-activity relationship software package as an in silico tool. The results showed that there was a structural alert (quinolone-3-carboxylic acid or naphthyridine analogue) in this impurity. Then the mouse lymphoma assay (MLA) and chromosome aberration assay in Chinese hamster lung (CHL) cells were conducted in vitro. Both assays were conducted in the presence or absence of S-9 mix. The test impurity was not mutagenic in the test of MLA. While there was a statistically significant increase in the number of metaphase CHL cells with structural aberrations at the concentration of 1 mg/mL with S-9 mix, and the aberrations rate is 6.5%. It did not significantly increase the number of structural aberration in CHL cells in the presence (at other two doses) or absence of S-9 mix. Based on these assays, levofloxacin n-oxide could be controlled as a non-genotoxic impurity despite the DEREK alert for quinolone-3-carboxylic acid or naphthyridine analogue.
journal_name
Toxicol Mech Methodsjournal_title
Toxicology mechanisms and methodsauthors
Zhu Q,Li T,Li J,Guo M,Wang W,Zhang Xdoi
10.3109/15376516.2011.635319subject
Has Abstractpub_date
2012-04-01 00:00:00pages
225-30issue
3eissn
1537-6516issn
1537-6524journal_volume
22pub_type
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