Liquid-liquid-solid Extraction Of Ofloxacin Enantiomer By Benzoyl-tartaric Acid Derivative

Levofloxacin is one of the most outstanding third-generation fluoroquinolone antibacterial drugs in the clinical efficacy and the curative effect is one of the best breed. It is widely used in the global medical markets. According to the experiments performed in vitro, levofloxacin’antibacterial activity is 8 to 128 times than R-ofloxacin, and 2 times of ofloxacin racemate. The antibacterial principle of levofloxacin is that it inhibit DNA gyrase transcription, such as enterobacteriaceae strains and staphylococcus aureus, in a result, levofloxacin exhibits an excellent antibacterial activity. S-(-)-OFLX compared to OFLX used in clinically has an advantage of lower dosage, fewer side effects and more efficacy.The use of chiral resolution techniques to obtain an optical purity S-OFLX is one of the hotest research topic in recent years. Chiral liquid liquid solid extraction separate ofloxacin racemate is based on chiral liquid-liquid extraction process, the aqueous phase is ofloxacin aqueous solution, the organic phase is alkanes, dibenzoyl tartaric acid derivatives is used as solid phase particle to liquid liquid solid extraction separation of ofloxacin enantiomers. This method not only inherits the merit of solvent extraction, such as simple operation, wide applicable range, low power consumption and continuous production, etc., but also achieves a good split effect and greatly improves the extraction efficiency. The maximum separation factor and enantiomer ee% can reach 5.3 and 65.61% respectively. With ofloxacin of ultra-solubility 1.6g/L in aqueous solution, the maximum separation factor and enantiomer ee% can achieve 8.5 and 76.32%.In this paper, high performance liquid chromatography is used to analysis aqueous solutions enantiomers of ofloxacin concentration after chiral extraction process. Specific conditions:C18 column and UV detection wavelength of 295nm, with 10mmol/L L-leucine and 5mmol/L CuSO4, water-methanol (85:15, V/V) solution as the mobile phase, mobile phase flow rate of 0.8 mL/min; injection volume:10μL, column column temperature is controlled at 39℃. This analytical method significantly reduces HPLC analysis time of ofloxacin enantiomers within 20min.With dibenzoyl tartaric acid derivatives used as chiral organic solid particles liquid liquid solid extraction separation of ofloxacin racemate, it is concluded:When solid chiral separation agents are enantiomers, separation factor are basically identical, L-chiral resolving agent’ selective extraction capacity of S-Ofl is the same as D-chiral resolving agent’selective extraction capacity of R-Ofl; but the chiral separation ability of DBTA is better than DTTA and DMTA. In the chiral liquid liquid solid extraction process, with the increases of ofloxacin feed concentration and the decreases of temperature, the split result is better.In this study, the use of cheap and easily accessibility dibenzoyl tartaric acid derivatives as chiral resolving agents, distribution behavior of ofloxacin enantiomers in organic phase, aqueous phase and solid phase have been studied. Liquid-liquid-solid extraction separation of racemate ofloxacin has realized the chiral separation progress. This method will promote the development of chiral drugs split in a certain sense, and it may provide a reference for further homochirality study.