Solid-phase microextraction: investigation of the metabolism of substances that may be abused by inhalation.
Purified liquefied petroleum gas (LPG), a mixture of butane, isobutane, and propane, is commonly abused by inhalation. Little is known about the mammalian metabolism of these substances. Metabolism of other hydrocarbons, including n-hexane and cyclohexane, has been studied in vitro using a range of liver preparations, with metabolites analyzed by static headspace techniques. Solid-phase microextraction (SPME) for sampling metabolites in the headspace of incubates of volatile compounds with activated rat liver microsomes is investigated. Cyclohexanol and cyclohexanone were formed from cyclohexane and 1-, 2-, and 3-hexanol and 2-hexanone from n-hexane as predicted. Secondary alcohols are found for the other compounds studied, except for propene and isobutane, together with 2-propanone and 2-butanone from propane and n-butane, respectively. Samples from three individuals who died following LPG abuse contained a range of putative n-butane metabolites: n-butanol, 2-butanol, 2,3-butanediol, 3-hydroxy-2-butanone, and 2,3-butanedione. To our knowledge, the last three compounds have not been proposed as metabolites of n-butane in man. These might be produced through similar metabolic pathways to those of n-hexane and n-heptane. The findings indicate the value of SPME for investigating the metabolism of volatile substances and for detecting and monitoring exposure to these compounds.
Walker
Richard
R
Department of Chemical Pathology, Southampton General Hospital, Tremona Road, Southampton, SO16 6YD, UK.
Flanagan
Robert J
RJ
Lennard
Martin S
MS
Mills
Graham A
GA
Walker
Valerie
V
D000818:Animals; D001344:Autopsy; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D013287:Illicit Drugs / Q000493:pharmacokinetics*; D019570:Inhalation Exposure; D008862:Microsomes, Liver / Q000378:metabolism; D051381:Rats; D012015:Reference Standards; D019966:Substance-Related Disorders / Q000378:metabolism*; D014835:Volatilization
D013287:Illicit Drugs