A rapid, sensitive electron-capture gas chromatographic procedure for analysis of metabolites of N-methyl,N-propargylphenylethylamine, a potential neuroprotective agent.
BACKGROUND
N-Methyl,N-propargyphenylethylamine (MPPE) is a novel analog of (-)-deprenyl, a drug prescribed for Parkinson's disease and shown to have neuroprotective and neurorescue properties in a wide variety of in vitro and in vivo models. MPPE is also neuroprotective, but has the advantage over (-)-deprenyl of not being metabolized to amphetamine or N-methylamphetamine.


METHODS
In this paper, extractive derivatization with pentafluorobenzenesulfonyl chloride (PFBSC) followed by electron-capture gas chromatography was utilized to study the metabolism of MPPE.


RESULTS
The procedure is rapid and reproducible, giving derivatives with excellent chromatographic properties. Using this procedure, it has now been shown that beta-phenylethylamine (PEA), N-methylphenylethylamine (N-methylPEA) and N-propargylphenylethylamine (N-propargylPEA) are formed from MPPE during incubation of this drug with human liver microsomes. Levels of all three metabolites were shown to increase with increasing time of incubation with the microsomes.


CONCLUSIONS
Extractive derivatization with PFBSC followed by electron-capture gas chromatography represents an efficient means of separating and quantitating the metabolites of MPPE, a novel neuroprotective agent.
Rittenbach
Kay
K
Neurochemical Research Unit, Department of Psychiatry, 1E7.31 Mackenzie Centre, University of Alberta, Edmonton, Alberta, Canada T6G 2R7. kar9@ualberta.ca
Sloley
B Duff
BD
Ling
Lei
L
Coutts
Ronald T
RT
Shan
Jackie
J
Baker
Glen B
GB
D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods*; D006801:Humans; D066298:In Vitro Techniques; D008694:Methamphetamine / Q000031:analogs & derivatives / Q000032:analysis / Q000378:metabolism; D008862:Microsomes, Liver / Q000378:metabolism; D018696:Neuroprotective Agents / Q000032:analysis* / Q000378:metabolism; D010627:Phenethylamines / Q000032:analysis / Q000378:metabolism; D012642:Selegiline / Q000031:analogs & derivatives* / Q000032:analysis* / Q000378:metabolism; D013450:Sulfones; D013997:Time Factors; D005464:Fluorobenzenes; D005466:Fluorocarbons
D008694:Methamphetamine; D018696:Neuroprotective Agents; D010627:Phenethylamines; D012642:Selegiline; D013450:Sulfones; C508639:N-Methyl,N-propargyphenylethylamine; C027141:N-methylphenethylamine; C029261:phenethylamine; C043853:pentafluorobenzenesulfonyl chloride; D005464:Fluorobenzenes; D005466:Fluorocarbons