Optimized HPLC technique for determining ciprofloxacin hydrochloride in infusion solutions

Abstract

Ciprofloxacin is a modern effective antibacterial drug widely used for the treatment of infectious disorders. The drug is available in various forms, including tablets, drops, capsules, and solutions. In serious cases, ciprofloxacin is administered in the form of dosed infusion preparations containing 200 mg of the parent drug in 100 ml of isotonic solution [1]. Foreign manufacturers prepare the infusions using ciprofloxacin base with lactic acid added as stabilizer. In some cases (ciprova, ciprofloxacin infusion solution from Lupin Laboratories Ltd., India), the preparation is additionally stabilized by adding sodium-EDTA salt.Russian manufacturers do not produce ciprofloxacin preparations in the form of solutions for infusion. Therefore, investigations in this direction are currently important. Since the State Register of Drugs includes only the parent compound of ciprofloxacin, it would be expedient to develop an infusion solution based on this substance. In order to proceed with this, it is necessary first to develop a reliable method for determining the drug in solution. According to published data [2], the most acceptable results can be obtained using HPLC. Indeed, this method in both reversed-and direct-phase variants has been successfully used for the quantitative determination of drugs belonging to the fluoroquinolone group. EXPERIMENTAL PARTBased on the results of preliminary experiments, we selected the following optimum composition of the infusion solution, which ensured required stability of the preparation: Ciprofloxacin hydrochloride 0.234 g Sodium chloride 0.9 g Citric acid 0.06 g Sodium hydrophosphate 0.1 g Water for injections to 100 mlThe HPLC procedure for the quantitative determination of ciprofloxacin hydrochloride in infusion solutions was developed using a liquid chromatograph of the Milikhrom-5 type equipped with a 2´80 mm column filled with Diasorb S-16 and a spectrophotometric detector tuned to 278 nm.According to published data [2 -4] on the HPLC analysis of fluoroquinolones, it is expedient to perform elution using solvent mixtures with acid components. In particular, Brkich [4] used a system with acetic acid. This was accompanied by the appearance of additional peaks in the chromatograms, which were explained by the peculiarities of ciprofloxacin adsorption on the HPLC column. However, we believe that the phenomenon observed in [4] was related to the existence of two forms of ciprofloxacin with different degrees of dissociation in solution. In such cases, it is expedient to use stronger acids such as phosphoric, which can provide for the complete protonation of nitrogen in the molecule of ciprofloxacin hydrochloride and for the suppression of ionization of the carboxy group.According to the U.S. Pharmacopoeia (USP-24), fluoroquinolones have to be eluted with a mixture of 0.025 M aqueous orthophosphoric acid solution (pH 3.0) and acetonitrile in a 87 : 13 ratio. We have used this solvent system and found that the peak of ciprofloxacin was asymmetric (the asymmetry coefficient calculat...