Abstract: A high performance liquid chromatographic (HPLC) method using cellulose tris-(3,5-dimethylphenylcarbamate) as chiral stationary phase (Lux Cellulose-1) for the separation of trantinterol hydrochloride enantiomers was developed. The method was based on normal phase model with n-heptane as the basal solvent of mobile phase. The influences of organic modifiers, mobile phase additives and column temperature on the retention and separation of the enantiomers were examined and discussed. It was demonstrated that the mobile phase additives had a dominant effect on the enantiomeric separation. No separation was observed with the addition of diethylamine only in the mobile phase, while the retention was increased and the enatiomeric separation was observed with the addition of trifluoroacetic acid. When both trifluoroacetic acid and diethylamine were added into the mobile phase, the enantioseparation was significantly improved with a resolution up to 4.0. Ethanol and isopropanol were investigated as the organic modifiers, and ethanol offered a better enatiomeric resolution for trantinterol hydrochloride. In the examined temperature range between 15 ℃ and 35 ℃ both separation factor and resolution were decreased with the increase of the column temperature. The optimized chiral HPLC method for the separation of trantinterol hydrochloride enantiomers involved a Lux Cellulose-1 column (250 mm×4.6 mm, 5 μm), a mobile phase of n-heptane/ethanol/trifluoroacetic acid/diethylamine (88:12:0.3:0.05, v/v/v/v) at a flow rate of 1.0 mL/min, a detection at 246 nm and a column temperature of 25 ℃. The method is simple and rapid for the enantiomeric impurity determination of (~)-trantinterol hydrochloride bulk samples.

Key words: cellulose derivative-based chiral stationary phase, enantiomeric separation, trantinterol hydrochloride, high performance liquid chromatography (HPLC)