出版社：Japanese Association of Forensic Science and Technology
摘要：In order to establish the method for discriminating between oral ingestion (internal use) and dermal absorption (external use) of diphenhydramine (DPH) using biological fluids, the excretion profiles of unchanged DPH and its metabolites in urine as well as time-course changes in blood concentration of DPH have been investigated. Urine and blood specimens were obtained from volunteer users of either the sleep-inducing drug Drewell tablet or the antipruritic drug New Restamin Kowa ointment. Unchanged DPH and its metabolites were identified and quantified using liquid chromatography-tandem mass spectrometry with a C 18 semi-micro column. DPH and its three metabolites, diphenhydramine N -oxide, N -desmethyl diphenhydramine and diphenhydramine N -glucuronide, have been detected, for the first time, in urine after dermal absorption, and the urinary excretion profiles of DPH and the metabolites were observed along with those after oral ingestion. Maximum concentration times of DPH and its metabolites in urine were between 21 and 73 hours in dermal absorption, and between 4 and 21 hours in oral ingestion. Maximum concentration times of DPH in blood for dermal absorption were also larger than those for oral ingestion. These results suggested that absorption of DPH through the skin occurs more slowly and continuously compared with oral ingestion. In addition, the maximum concentrations of DPH and its metabolites in urine after oral ingestion were ten to hundred times higher than those after dermal absorption, which suggests that the urinary concentration of DPH and its metabolites could be applicable as the indexes which allow to discriminate between internal and external uses. The findings obtained in this study will be indispensable as the fundamental information for discussing intake situations of DPH in the forensic fields.
关键词：Diphenhydramine;Discrimination between internal and external uses;Urinary excretion profile;LC-MS/MS;Dermal absorption
