Sarafloxacin is a quinolone antibiotic drug, which was removed from clinical use by its manufacturer Abbott Laboratories from April 30, 2001. Chemically it is a fluoroquinolone that inhibits bacterial DNA gyrase and topoisomerase IV, producing bactericidal activity against many Gram negative organisms and selected Gram positive strains. The substance was developed for oral administration and characterized by good tissue penetration, concentration dependent killing and post antibiotic effect; pharmacokinetic profiling reported oral absorption with distribution to peripheral tissues, hepatic metabolism and renal elimination. Analytical and formulation work on sarafloxacin focused on stability under acidic and oxidative conditions, photostability, and control of piperazine-related impurities; routine quality control employed HPLC with UV detection and LC-MS for identification of related substances.
Parent: Sarafloxacin
Typical quality specifications used in analytical control of sarafloxacin set numerical acceptance criteria consistent with ICH guidance: individual specified related substances are commonly limited to 0.2 percent w by weight or lower, any unspecified impurity is typically controlled below 0.1 percent w by weight, and total impurities are generally limited to 1.0 percent w by weight. Known related compounds and degradation products encountered in manufacture and stability studies include desethyl-sarafloxacin, sarafloxacin N-oxide (piperazine N-oxide), ring-hydroxylated products such as 8-hydroxy-sarafloxacin, deaminated derivatives and decarboxylation products; limits for some identified degradants have been set at 0.05 to 0.5 percent depending on toxicological assessment and identification status. Residual genotoxic or mutagenic impurities are controlled to thresholds defined by ICH M7 and assessed by LC-MS and orthogonal techniques such as NMR when identification is required.
Sarafloxacin was developed as a broad spectrum fluoroquinolone antibiotic for treatment of bacterial infections by inhibiting DNA gyrase and topoisomerase IV; it was prescribed for respiratory and urinary tract type infections in development and early clinical use but was removed from clinical use by its manufacturer Abbott Laboratories on April 30, 2001.
