Oxolinic acid is a quinolone antibiotic developed in Japan in the 1970s. Dosages 12 to 20 mg/kg orally administered for five to ten days. The antibiotic works by inhibiting the enzyme DNA gyrase, binding to the gyrase-DNA complex and preventing relaxation of supercoiled DNA which leads to inhibition of bacterial replication and bactericidal activity against susceptible Gram negative and some Gram positive organisms. Chemically it is a small molecule quinolone with typical physicochemical properties of the class including moderate lipophilicity and limited water solubility; it shows moderate oral bioavailability, predominant renal excretion of parent drug and metabolites, and a plasma protein binding profile consistent with distribution into peripheral tissues. In addition to its antibacterial action, oxolinic acid has been reported to act as a dopamine reuptake inhibitor and to exhibit stimulant like central nervous system effects at higher exposure; these CNS pharmacology observations correlate with affinity for monoamine transporters in vitro. Analytical characterization commonly uses HPLC with UV detection for assay and related-substance profiling, LC-MS for structural assignment of impurities and degradants, and forced-degradation studies to define hydrolytic, oxidative and photolytic pathways.
Parent: Oxolinic Acid
Parent: Oxolinic acid
Typical quality specifications and impurity limits for oxolinic acid raw material and formulated material are set to control both process-related and degradation-related species; a representative specification would limit individual identified related compounds to not more than 0.2 to 0.5 percent weight by weight and total related substances to not more than 1.0 percent weight by weight, consistent with ICH Q3A/Q3B risk-based approaches. Common related compounds detected by LC-MS and HPLC include N-oxide derivatives, 7-hydroxy or 3-hydroxy oxidation products, decarboxylated degradants, ring-opened cleavage products and O- or N-dealkylation impurities derived from synthetic steps. Residual solvents used in manufacture are controlled to acceptable ppm levels, for example methanol not more than 3000 ppm and acetonitrile not more than 410 ppm when applicable, and elemental impurities are controlled by limits such as not more than 10 to 20 ppm for class 1 and 2 metals depending on the process route. Release and stability testing normally specify identification and quantitation by validated HPLC-UV methods, LC-MS confirmation for unknowns above reporting thresholds, and acceptance criteria for assay, related substances, residual solvents and heavy metals.
Oxolinic acid is used as an antibacterial agent historically in veterinary and aquaculture settings and in some human uses in earlier decades; it is effective against a range of Gram negative pathogens and selected Gram positive organisms by inhibiting DNA gyrase and preventing bacterial DNA replication.
Treatment protocols in aquaculture typically use oxolinic acid administered orally via medicated feed at 12 to 20 mg/kg body weight once daily for five to ten days depending on species and clinical response; proper water quality management, dosing accuracy, withdrawal periods and regulatory approvals must be observed, and susceptibility testing should guide use to limit resistance development.
The chemical formula for oxolinic acid is C13H9NO4.
