Identification of diphenhydramine metabolites in human urine by capillary electrophoresis-ion trap-mass spectrometry

被引:27
作者
Baldacci, A [1 ]
Prost, F [1 ]
Thormann, W [1 ]
机构
[1] Univ Bern, Dept Clin Pharmacol, CH-3010 Bern, Switzerland
关键词
desmethyldiphenhydramine; diphenhydramine-N-oxide; diphenylmethoxyacetic acid-glycine amide;
D O I
10.1002/elps.200305829
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
The identification of diphenhydramine (DH) metabolites that are frequently observed in the capillary zone electrophoresis (CZE) and micellar electrokinetic capillary chromatography (MEKC) analyses of alkaline liquid/liquid and solid-phase extracts of patient urines is demonstrated. Having standards for DH and diphenhydramine-N-oxide (DHNO), the presence of these two compounds could be confirmed in urines that were collected overnight after administration of 25 mg DH chloride. Using CZE coupled to ion-trap mass spectrometry (CE-MSn) with positive electrospray ionization and an acetate buffer at pH 5.6, the [M+H](+) ions of DH (m/z = 256), DHNO (m/z = 272), and nordiphenhydramine (NDH, m/z = 242) and their fragmentation to a common m/z 167 product ion (diphenylcarbinol moiety) was monitored. The data indicate that all three compounds are cations in an acidic environment, the migration order being NDH, DH, and DHNO. Data obtained under negative electrospray ionization conditions suggest the presence of diphenylmethoxyacetic acid-glycine amide ([M-H](-) ion of m/z 298 and fragmentation to m/z 254, loss of CO2), a metabolite that could tentatively be assigned to a characteristic peak observed in the MEKC electropherogram at alkaline pH. The data presented in this paper illustrate the value of using CE-MSn for identification of urinary drug metabolites for which no standards are available.
引用
收藏
页码:1607 / 1614
页数:8
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