Study of the stability of promethazine enantiomers by liquid chromatography using a vancomycin-bonded chiral stationary phase.

Three chiral stationary phases based on macrocyclic antibiotics (teicoplanin, vancomycin and ristocetin A) have been tested for chiral separations of promethazine. The vancomycin phase permits the best, baseline enantioseparation of promethazine, with a mobile phase of a 80:20 (v/v) mixture of methanol with a 1% aqueous triethylamine acetate buffer of pH 4.1 and with the analysis time not exceeding 15 min. The limits of detection amount to 27.5 and 31.0 ng/ml for the earlier and later eluting enantiomers, respectively. This separation system, that also permits a sufficient resolution between the promethazine enantiomers and their degradation products, has further been used for the monitoring of the effects of light, temperature and the promethazine concentration in solution on the stability of methanolic promethazine solutions over a period of 19 days. It has been found that the stability of more concentrated solutions is primarily affected by the temperature, whereas the effects of the temperature and light are comparable with more dilute solutions. After 19 days, a solution of 0.5 mg/ml promethazine stored in darkness at a low temperature still contained 84.0% of the original amount of the enantiomers; this value was 89.6% for a solution with the ten times lower promethazine concentration. If the solutions were stored in darkness but at laboratory temperature, the respective values decreased to 38.1 and 62.6% and for the solutions exposed to light at laboratory temperature they decreased even more to 36.7 and 52.6% of the initial promethazine amount.