US EPA

1187952 

Journal Article 

Preparation of N-demethylated drug metabolites for analytical purposes using 1-chloroethyl chloroformate 

Pelander, A; Ojanpera, I; Hase, TA 

1997 

Yes 

Forensic Science International
ISSN: 0379-0738
EISSN: 1872-6283 

ELSEVIER SCI IRELAND LTD 

CLARE 

85 

3 

193-198 

English 

10.1016/S0379-0738(96)02088-9 

WOS:A1997WV91500003 

http://www.sciencedirect.com/science/article/pii/S0379073896020889
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Potential reagents for the N-demethylation of tertiary amines were screened in order to produce drug metabolite reference material for forensic toxicological applications, and 1-chloroethyl chloroformate was found to be the reagent of choice. The reaction was performed by refluxing in dry 1,2-dichloroethane under nitrogen, and the carbamate intermediate was hydrolysed by treatment with methanol. The products were purified by preparative layer chromatography, and their structures were confirmed by gas chromatography-mass spectrometry and by thin layer chromatography using derivatization with Fast Black K salt. The five drugs investigated, promazine, levomepromazine, orphenadrine, clomipramine and chlorprothixene, N-demethylated smoothly and the yields of the purified products were between 40 and 60% from 20 mg of the starting compound. 

demethylation; drug metabolite; 1-chloroethyl chloroformate