Detection and time course of cocaine N-oxide and other cocaine metabolites in human plasma by liquid chromatography/tandem mass spectrometry.
Gas chromatography/mass spectrometry (GC/MS) is often used for detection and measurement of cocaine metabolites in biological specimens. However, cocaine N-oxide, a recently identified metabolite of cocaine, is thermally degraded when introduced into a GC/MS. The major degradation products are cocaine and norcocaine. When cocaine N-oxide was measured in rat plasma using liquid chromatography in combination with electrospray ionization-mass spectrometry (LC/ESI-MS), the cocaine N-oxide concentrations in the rat plasma were reported to be as high as 30% of the cocaine concentrations. However, in our study involving LC/ESI-MS/MS analysis of plasma collected from human subjects following administration of oral cocaine, we determined that the concentrations of cocaine N-oxide relative to the cocaine concentrations never exceeded 3%. This suggests that determination of cocaine concentration in human plasma by GC/MS analysis will not significantly distort the actual cocaine concentrations due to thermal conversion of cocaine N-oxide to cocaine. In the work reported here, we compared results obtained using GC/MS, LC/ESI-MS/MS, and liquid chromatography/atmospheric pressure chemical ionization-tandem mass spectrometry (LC/APCI-MS/MS) to determine thermal degradation of cocaine N-oxide. LC/ ESI-MS/MS was selected to determine cocaine, benzoylecgonine, and cocaine N-oxide, and LC/APCI-MS/MS was selected to determine ecgonine methyl ester and norcocaine in plasma collected from three human subjects participating in a clinical study. The resulting time course data provide additional information into kinetic interrelationships between cocaine N-oxidation and cocaine hydrolysis.
Lin
Shen-Nan
SN
University of Utah Center for Human Toxicology, 20S 2030E, Room 490, Salt Lake City, Utah 84112-9457, USA. shen-nan.lin@hsc.utah.edu
Walsh
Sharon L
SL
Moody
David E
DE
Foltz
Rodger L
RL
D000818:Animals; D003042:Cocaine / Q000031:analogs & derivatives / Q000097:blood* / Q000378:metabolism; D003497:Cyclic N-Oxides / Q000097:blood; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods*; D006801:Humans; D007700:Kinetics; D051381:Rats; D013696:Temperature; D013997:Time Factors
D003497:Cyclic N-Oxides; C486959:cocaine N-oxide; D003042:Cocaine