An HPLC-ESI-MS method for simultaneous determination of fourteen metabolites of promethazine and caffeine and its application to pharmacokinetic study of the combination therapy against motion sickness.

The combination therapy, promethazine and caffeine had been proven effective in treating motion sickness and counteracting some possible side effects of using promethazine alone while the mechanism and interaction remained unclear. Therefore, an HPLC-ESI-MS method for simultaneous determination of both drugs, and their metabolites was developed for purpose of pharmacokinetic study. To determine as many metabolites as possible, the influence of parameters such as column, flow rate and pH value of mobile phase, ionization polarity and fragmentation voltage were optimized.