Identification of Two Novel Cocaine Metabolites in Bile by Gas Chromatography and Gas Chromatography/Mass Spectrometry in a Case of Acute Intravenous Cocaine Overdose

Lowry, W. T.; Lomonte, J. N.; Hatchett, Don; Garriott, James C.

doi:10.1093/jat/3.3.91

Cited by 29 publications

(11 citation statements)

References 4 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In vitreous humor, however, cocaine was detected at concentrations higher than those of BEG and EME by a factor of 1.6 and 2.5, respectively. The drug levels in bile are consistent with those reported by Agarwal and Lemos (1996), but not with those of other authors (Vanbinst et al, 2002;Lowry et al, 1979;Furnari et al, 2002). The cocaine levels in vitreous humor are similar to those obtained by Mackey-Bojack et al (2000) and McKinney et al (1995), but substantially higher than those reported by Logan and Stafford (1990).…”

Section: Resultssupporting

confidence: 87%

“…Cocaine, BEG and EME levels from patients intoxicated Case EME (µg ml Cocaine and its metabolites could be determined jointly in both bile and vitreous humor samples from only 12 individuals. The analyte concentrations thus obtained exhibited poor correlation (r < 0.2) between bile and vitreous humor; the average bile-to-vitreous humour concentration ratios were 0.5 for cocaine, 4.5 for BEG and 3.3 for EME; the value for BEG was similar to that obtained by Furnari et al (2002), but that for the parent drug departs from those reported by Poklis et al (1987) and Lowry et al (1979). A total of 19 bile samples and 21 vitreous humor samples were found to contain the three analytes.…”

Section: Resultscontrasting

confidence: 52%

See 1 more Smart Citation

GC-FID determination of cocaine and its metabolites in human bile and vitreous humor

et al. 2006

View full text Add to dashboard Cite

Gas chromatography was used in combination with flame ionization detection (GC-FID) to develop a method for determining cocaine and its two metabolites, benzoylecgonine (BEG) and ecgonine methyl ester (EME), in bile and vitreous humor. The method used a 12 m x 0.2 mm i.d. column of 0.33 microm film thickness packed with 5% phenylmethylsiloxane, and proadifen as a reference compound. Drug-free bile and vitreous humor samples were used to prepare solutions of the target compounds at concentrations over the range 0.1-4 microg ml(-1) that were subjected to solid-phase extraction through Bond Elut Certify columns and derivatized with 99:1 (v/v) N,O-bis-trimethylsilyltrifluoroacetamide (BSTFA)/trimethylchlorosilane (TMCS). Calibration graphs were highly linear, with correlation coefficients above 0.99 in all instances. Also, the precision of the method was found to be quite acceptable, with coefficients of variation less than 5% for bile and less than 7% for vitreous humor. The average extraction yields ranged from 73.6% to 91.2% for bile and from 71.5% to 92.2% for vitreous humor. The proposed method was used to analyse 26 samples of bile and as many of vitreous humor from individuals fatally poisoned by cocaine, whether alone or in combination with other drugs. The mean drug levels found were 0.75 and 1.54 microg ml(-1) for cocaine in bile and vitreous humor, respectively, 6.35 and 0.94 microg ml(-1) for BEG, and 2.18 and 0.61 microg ml(-1) for EME.

show abstract

Section: Resultssupporting

confidence: 87%

Section: Resultscontrasting

confidence: 52%

GC-FID determination of cocaine and its metabolites in human bile and vitreous humor

et al. 2006

View full text Add to dashboard Cite

show abstract

“…Cocaine is N-demethylated to norcocaine and further converted to N-hydroxynorcocaine. The presence of norcocaine has been demonstrated in man (Inaba et al 1978;Jindal et al 1978;Lowry et al 1979), whereas N-hydroxynorcocaine has been identified in rats and mice only (Evans 1983;Shuster et al 1983;Jindal and Lutz 1986;Benuck et al 1988). When administered to mice at equimolar doses, norcocaine was demonstrated to be more hepatotoxic than the cocaine parent molecule, and N-hydroxynorcocaine was the most potent species of all (Thompson et al 1979).…”

Section: Metabolic Pathwaysmentioning

confidence: 99%

“…Furthermore, analysis by GC-MS of human urine and bile revealed ecgonidine methylester (Lowry et al 1979) and ecgonidine (Zhang and Foltz 1990) as additional metabolites of cocaine. The formation of these compounds is poorly understood.…”

Section: Metabolic Pathwaysmentioning

confidence: 99%

Biomechanisms of cocaine-induced hepatocyte injury mediated by the formation of reactive metabolites

Boelsterli

Göldlin

1991

Arch Toxicol

View full text Add to dashboard Cite

Cocaine is an intrinsic hepatotoxin in laboratory animals, and there is growing evidence that high doses of cocaine can precipitate hepatic necrosis in humans. The rodent model of cocaine hepatotoxicity is commensurate with the concept that a multistep mainly cytochrome P-450 dependent N-oxidative pathway is responsible for the expression of hepatocellular injury. Among the possible biomechanisms by which cocaine exerts its cytotoxic effects, direct oxidative damage by reactive oxygen species generated by redox cycling during the metabolic cascade seems most important. The role of the ensuing lipid peroxidation and protein thiol oxidation is less clear. Similarly, the functional role of irreversible (covalent) binding of a not yet defined electrophilic cocaine intermediate to hepatocellular proteins remains enigmatic so long as the critical molecular targets have not been identified. Finally, glutathione plays a pivotal protective role against cocaine-induced hepatic injury. Interactions with ethanol or inducers of the expression of the cytochrome P-450IIB subfamily can potentiate cocaine hepatotoxicity. Thus, the net amount of the ultimate reactive species seems to determine the severity of the hepatic lesions and to be responsible for the marked interspecies, interstrain, and sex differences. Recent advances in culture techniques of hepatocytes and precision-cut liver slices from various species including man have made it possible to correlate cocaine biotransformation with cytotoxicity and to selectively study the putative cellular mechanisms. Clearly, more studies are necessary to further illuminate our understanding of the role of the biochemical and molecular events precipitating hepatic necrosis during cocaine-mediated hepatotoxicity.

show abstract

“…The cocaine concentrations for our series are similar to other previously reported values, 9,15,16 but different from those obtained by other authors. 8,17,18 Blood samples from 15 individuals fatally poisoned with cocaine in our series were analyzed by radioimmunoassay in parallel to the bile samples. The drug levels in bile invariably exceeded those in blood; the ratio between the two ranged from 2.2 to 470.6 (average 64.8).…”

Section: Resultsmentioning

confidence: 99%

Bile Analysis for Cocaine and Benzoylecgonine in Overdose Cases

Fernández¹,

Aldonza²,

Bermejo³

et al. 2008

Journal of Liquid Chromatography & Related Technologies

View full text Add to dashboard Cite

A method for determining cocaine and benzoylecgonine (BEG) in human bile using high performance liquid chromatography (HPLC) with ultraviolet detection at 235 nm is proposed. The method uses a Lichrospher RP18 column and methanol-phosphate buffer as mobile phase. Following solid phase extraction with Bond Elut Certify cartridges, the linearity of the method was examined over the analyte concentration range 0.125-5 g/mL in bile. The precision of the method was acceptable, with coefficients of variation less than 5%. The average extraction yield was 82% for cocaine and 76% for BEG. The proposed method was applied to 30 bile samples from individuals fatally poisoned with cocaine.

show abstract

Identification of Two Novel Cocaine Metabolites in Bile by Gas Chromatography and Gas Chromatography/Mass Spectrometry in a Case of Acute Intravenous Cocaine Overdose

Cited by 29 publications

References 4 publications

GC-FID determination of cocaine and its metabolites in human bile and vitreous humor

GC-FID determination of cocaine and its metabolites in human bile and vitreous humor

Biomechanisms of cocaine-induced hepatocyte injury mediated by the formation of reactive metabolites

Bile Analysis for Cocaine and Benzoylecgonine in Overdose Cases

Contact Info

Product

Resources

About