β-cyclodextrin(β-CD) and its derivatives, hydroxypropyl β-cyclodextrin (Hp-β-CD) and sulfated β-cyclodextrin (S-β-CD) were evaluated as chiral mobile phase additives for enantioseparation of few active pharmaceutical ingredients (APIs), salbutamol, etodolac, ofloxacin, milnacipran (MIL), fluoxetine (FLU), hydroxyzine (HYZ), and formoterol (FM). RP-HPLC was used for method development wherein chiral selector was added to the mobile phase and separation was achieved on the achiral C8 column, without using costly chiral columns. During HPLC method development, the parameters affecting separations such as type and concentration of chiral selector, pH of the mobile phase, concentration of buffer, type of achiral column (fully porous and core-shell silica columns), were investigated for optimum resolution. The chromatographic performance of the column packed with 5 µm core-shell silica (Phenomenex, Kinetex C8) was compared with the column packed with 5 µm fully porous silica (Phenomenex, HyperClone C8). β-CD and Hp-β-CD were not able to separate enantiomers of any of the above-mentioned APIs, while S-β-CD was able to separate enantiomers of MIL, FLU, HYZ, and FM. On the HyperClone C8 column, the enantiomers of MIL, FLU, HYZ, and FM were separated with the resolution of 1.76, 2.29, 2.26, and 2.91 in the run-time of 8, 10, 22, and 14 minutes respectively. Whereas on the Kinetex C8 column, the enantiomers of MIL, FLU, HYZ, and FM were separated with the resolution of 2.96, 2.62, 3.33, and 2.57 in the run-time of 5, 5, 5.5, and 8 minutes, respectively. The application of an achiral core-shell silica column led to faster elution with excellent system suitability parameters. It reduced analysis time and the consumption of S-β-CD significantly. The developed methods were validated as per ICH guidelines. The validated methods were applied for the enantiomeric purity determination of active pharmaceutical ingredients in the marketed formulation.

RP-HPLC enantioseparation of few active pharmaceutical ingredients made simple and cost-effective by using achiral core-shell silica column and sulfated beta-cyclodextrin as chiral mobile phase additive

ACS Spring Meeting 2021

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