Separation of Ketorolac enantiomers on polysaccharide‐based chiral stationary phases using a polar organic mobile phase

Abstract

Ketorolac has been widely applied in clinical medicine for its antipyretic, analgesic and anti‐inflammatory pharmacological activity. Research showed that the analgesic effect of the S enantiomer is 230 times stronger than that of the R enantiomer. Getting the high‐purity S enantiomer of Ketorolac has profound significance but still remains a challenging topic. In this work, the separation of the R and S enantiomers of Ketorolac was investigated on polysaccharide‐based chiral stationary phases. Chiralcel AD‐H, OD‐H, OJ‐H and AS‐H columns were evaluated using polar organic and normal phase mode, respectively, in which the OJ‐H column showed the best performance with high selectivity and resolution for Ketorolac with α = 2.43 and RS = 9.04 by using methanol/formic acid (100:0.1, v/v) as the mobile phase. The influences of acid additive, composition of mobile phase and temperature were examined. The coating amount of cellulose tris‐(4‐methylbenzoate) has significant influence on the sample loadability. The high loadability of chiral stationary phases coated with 40% of cellulose tris‐(4‐methylbenzoate) allows preparative separation up to 16 mg on an analytical column of 250 × 4.6 mm id in a single run for Ketoroac using methanol/formic acid (100:0.1, v/v) as mobile phase, which shows a potential application in industrial preparation.

Efficient preparative separation of 6‐(4‐aminophenyl)‐5‐methyl‐4, 5‐dihydro‐3(2H)‐pyridazinone enantiomers on polysaccharide‐based stationary phases in polar organic solvent chromatography and supercritical fluid chromatography

“…As shown in Figure A, a typical U‐shape curve of k versus percentage of ACN was obtained, with a lowest point at about 60–70%. This phenomenon could also be observed in some reported results . At high content of ACN (here above 70%), the retention increased with a decrease in polar MeOH, indicating a normal phase behavior .…”

“…The huge market demand of chiral drugs promotes other chromatographic techniques for the purification of enantiomers such as polar organic solvent chromatography (POSC) and supercritical fluid chromatography (SFC). POSC gets growing attention recently , where only polar organic solvents such as alcohols, acetonitrile, and their mixtures are used as mobile phase, which can bring some benefits such as a short separation time, a high column efficiency and commonly a better solubility of solutes in the mobile phase . SFC is now well known for its fast analysis and green mobile phase that consists of carbon dioxide (CO 2 ) and organic modifier (normally <40%) .…”

Enantiomeric analysis of simendan on polysaccharide‐based stationary phases by polar organic solvent chromatography

“…Subsequently, with MeOH percentages higher than 70% (v/v), π–π stacking interactions seemed to be enforced [29], where the k value increased with decreasing ACN content. A similar trend was also observed in recent studies [24,25].…”

“…In this mode, only polar organic solvents such as alcohols, ACN, and their mixtures are used as the mobile phase, which has advantages such as short analysis time, high efficiency, favorable peak shape, and improved solubility of analytes [20–22]. Recently, the applicability of polysaccharide‐based CSPs in combination with POSC has successfully resolved many chiral compounds, such as racecadotril, ketorolac, an intermediate of levosimendan, and some carboxylic acid derivatives [23–26], demonstrating their excellent enantiomer separation potential.…”

Liquid chromatographic enantioseparation, determination, bioassay and isolation of enantiomers of Ketorolac: A review

“…He et al, [42] (with 10, 20, 30 and 40% of CTMB) were prepared according to the literature reports [43]. The packing material thus obtained was suspended in methanol and packed in stainless-steel tubes (250 mm x 4.6 mm i.d.)…”