Simultaneous determination of dimethylamphetamine and its metabolites in rat hair by gas chromatography-mass spectrometry

In order to study the disposition of dimethylamphetamine (DMAP) and its metabolites, DMAP N-oxide, methamphetamine (MA) and amphetamine (AP), from plasma to hair in rats, a simultaneous determination method for these compounds in biological samples using gas chromatography-mass spectrometry with selected ion monitoring (GC-MS-SIM) was developed. As DMAP N-oxide partially degrades to DMAP and MA during GC-MS analysis, it was necessary to avoid conditions which co-extract the N-oxide in the sample preparation so as to assure no contribution of artifactual products from DMAP N-oxide in the detection of the other compounds. For confirmation of the satisfactory separation of DMAP N-oxide from the others, the internal standards used for quantification were labeled with different numbers of deuterium atoms. Determination of unchanged DMAP was performed without any derivatization, that of DMAP N-oxide was carried out after conversion into trifluoroacetyl-MA by reaction with trifluoroacetic anhydride, and MA and AP were quantified after trifluoroacetyl-derivatization. After intraperitoneal administration of DMAP HCl to pigmented hairy rats (5 mg kg(-1) day(-1), 10 days, n=3), concentrations of DMAP and its metabolites in urine, plasma and hair were measured by GC-MS-SIM. The area under the concentration versus time curves (AUCs) of DMAP, DMAP N-oxide, MA and AP in the plasma were 397.2+/-97.5, 279.7+/-68.3, 18.4+/-1.2 and 15.9+/-2.2 mu g min ml(-1), while their concentrations in the hair newly grown for 4 weeks after administration were 4.82+/-0.67. 0.45+/-0.09, 3.25+/-0.36 and 0.89+/-0.05 ng mg(-1), respectively. This fact suggested that the incorporation tendency of DMAP N-oxide from plasma into hair was distinctly low in comparison with the other compounds. (C) 2000 Elsevier Science B.V. All rights reserved.