Discrimination between internal and external uses by analysis of urine and blood from diphenhydramine users

 STAGE DOI: 10.3408 / jafst.773 ) In order to establish the method for discriminating between oral ingestion ( internal use ) and dermal absorption ( external use ) of diphenhydramine ( DPH ) using biological ‰uids, the excretion proˆles of unchanged DPH and its metabolites in urine as well as time-course changes in blood concentration of DPH have been inves-tigated. 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 and its metabolites were identiˆed and quantiˆed 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 ˆrst time, in urine after dermal absorption, and the urinary excretion proˆles 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 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 ˆndings obtained in this study will be indispensable as the fundamental in-formation for discussing intake situations of DPH in the forensic ˆelds.