School of Pharmacy, East China University of Science and Technology, Shanghai 200237, PR China.
J Pharm Biomed Anal. 2012 Mar 25;62:119-28. doi: 10.1016/j.jpba.2011.12.033. Epub 2012 Jan 4.
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. Fourteen target analytes were well separated and all of them could be identified and determined in plasma after administration of promethazine and caffeine. The LODs and LOQs were 0.9-6.0 and 2.50-16.0 ng/ml, respectively; the recoveries of three levels of quality control samples were from 86.7% to 102%; the intra-day and inter-day precisions were less than 3% and 9%, separately; and the RSDs of compound stability were all lower than 10% within 24h after sample preparation. As a pharmacokinetic study of the combination therapy in 30 healthy volunteers, concentration-time curves of the drugs and metabolites were studied. The present method for simultaneous measurement of more than ten metabolites is valuable for the study of mechanism and interaction of the combination therapy.
联合治疗，异丙嗪和咖啡因已被证明在治疗晕动病和抵消一些单独使用异丙嗪的可能的副作用方面是有效的，而其机制和相互作用仍不清楚。因此，开发了一种用于同时测定两种药物及其代谢物的 HPLC-ESI-MS 方法，以进行药代动力学研究。为了尽可能多地确定代谢物，优化了柱、流动相的流速和 pH 值、电离极性和碎裂电压等参数的影响。在给予异丙嗪和咖啡因后，可分离并鉴定出 14 种目标分析物。LODs 和 LOQs 分别为 0.9-6.0 和 2.50-16.0ng/ml；三个质量控制样品水平的回收率为 86.7%至 102%；日内和日间精密度分别小于 3%和 9%；在样品制备后 24 小时内，化合物稳定性的 RSD 均低于 10%。作为 30 名健康志愿者联合治疗的药代动力学研究，研究了药物和代谢物的浓度-时间曲线。用于同时测定十多种代谢物的本方法对于联合治疗的机制和相互作用的研究具有重要价值。
