Cocaine metabolites

Katz, J.I., Terry, P., and Witkin, J.M., Comparative behavioral pharmacology and toxicology of cocaine and its ethanol-derived metabolite, cocaine ethyl-ester (cocaethylene), Life Sci., 50, 1351, 1992. 

EME and BEG, which is mainly obtained by enzymatic hydrolysis, represents respectively the 32-49 % and 29 45 % of total urinary metabolites cocaine can be converted, in small amounts, to norcocaine (NCOC) and psychoactive metabolite norbenzoylecgonine (NBE). The combined intake of alcohol and cocaine determines the formation of a pharmacologically active metabolite, the cocaethylene (ethyl ester of benzoylecgonine, CE), with a significant liver toxicity [13],... 

More recently Wang et al. have proposed analytical methods involving the use of UHPLC-MS/MS to determine four opiates and metabolites, live amphetamines, flunitrazepam and its two metabolites, cocaine and its four metabolites in OF. Samples were collected by spitting in a tube, then the fluids were diluted with twice the amount of distilled and deionized water and vortexed for 30 s. Liquid chromatography was performed with a gradient elution and the total run time was 7.5 min. The authors compared ESI, APCI, and APPI. The ion suppression ranged from 45 to 89 % and from 74 to 96 % on APCI and APPI, respectively. The authors... 

Miller El, Wylie FM, Oliver JS. Simultaneous detection and quantification of amphetamines, diazepam and its metabolites, cocaine and its metabolites, and opiates in hair by LC-ESI-MS-MS using a single extraction method. J Anal Toxicol 2008 32(7) 457-69. 

Cocaine metabolites (e.g., ecogonine, benzoylecogonine, etc.) 30 m DB-5 column, 200-280° at 107min. (Preparation of methyl ester and TMS derivatives is recommended.)... 

Methadone metabolites, methadone, cocaine (underivatized). morphine, and heroin... 

Methylphenidate like cocaine largely acts by blocking reuptake of monoamines into the presynaptic terminal. Methylphenidate administration produces an increase in the steady-state (tonic) levels of monoamines within the synaptic cleft. Thus, DAT inhibitors, such as methylphenidate, increase extracellular levels of monoamines. In contrast, they decrease the concentrations of the monoamine metabolites that depend upon monoamine oxidase (MAO), that is, HVA, but not catecholamine-o-methyltransferase (COMT), because reuptake by the transporter is required for the formation of these metabolites. By stimulating presynaptic autoreceptors, methylphenidate induced increase in dopamine transmission can also reduce monoamine synthesis, inhibit monoamine neuron firing and reduce subsequent phasic dopamine release. 

Overall, elimination of cocainic compounds has been observed to be the most efficient under CAS treatment (above 90% in most cases), compared to the rest of the investigated drugs of abuse and metabolites. However, they are not or... 

Bijlsma L, Sancho JV, Pitarch E, Ibanez M, Hernandez F (2009) Simultaneous ultra-high-pressure liquid chromatography-tandem mass spectrometry determination of amphetamine and amphetamine-like stimulants, cocaine and its metabolites, and a cannabis metabolite in surface water and urban wastewater. J Chromatogr A 1216(15) 3078-3089... 

Analysis of cocaine and its principal metabolites in waste and surface water using... 

Van Nuijs ALN, Pecceu B, Theunis L, Dubois N, Oiarlier C, Jorens PG, Bervoets L, Blust R, Neels H, Covaci A (2009) Cocaine and metabolites in waste and surface water across Belgium. Environ Pollut 157(1) 123-129... 

Table 1 provides the urinalysis test results for the 4,847 arrestees, While PCP was tested for by an EMIT test only, cocaine, opiates and methadone were tested for by both EMIT and thin layer chromatography (TLC). (The EMIT test for opiates is not specific to morphine, the metabolite of heroin, and can detect the recent use of a variety of opiates. A specimen positive for opiates is most likely to indicate the use of heroin in this population, however.) Our analyses will use only the results from the EMIT tests, because we have learned that the TLC general drug screen is less sensitive for detecting recent use of these illicit street drugs (Wish et al. 1983 Wish et al. 1984). 

PECs also were calculated by Domenech et al. [47] for determining the presence of cocaine and its main metabolite (benzoilecgonine) in different environmental compartments (air, water, soil, etc.). 

Cocaine and its metabolite Air, water, soil, sediments and Regional environmental benzoilecgonine (BE) suspended matter system... 

Jatlow, P., Elsworth, J.D., Bradberry, C.W., Winger, G., Taylor, J.R., Russell, R., and Roth, R.H., Cocaethylene a neuropharmacologically active metabolite associated with concurrent cocaine-ethanol ingestion, Life Scl, 48, 1781, 1991. 

Use of a catalytic cocaine antibody may bypass this potential downfall of the active immunization approach. The enzymatically active catalytic cocaine antibody cleaves cocaine into two inactive metabolites ecognine methyl ester and benzoic acid. The two metabolites are released from the catalytic antibody rendering the antibody free to degrade more cocaine. Because the... 

Mule S., Jukofshy D., Kogan M., Pace A., De Verebey K. Evaluation of the radioimmunoassay for benzoylecgonine (a cocaine metabolite) in human urine. Clin. Chem. 23 796, 1977. 

Up to 16 illicit drugs and metabolites belonging to five different chemical classes (cocainics, cannabinoids, opioids, amphetamine-like, and lysergic compounds) were analyzed in the collected samples. High purity (>97%) standard solutions... 

As it can be observed in Fig. 2, three out of the 16 investigated compounds, namely, heroin, lysergic acid diethylamide (LSD), and its metabolite 2-oxo, 3-hydroxy-LSD (O-H-LSD), were not detected in any wastewater sample. Two other target analytes, 6-acetyl morphine (6ACM) and A9-tetrahydrocannabinol (THC), were only present in influent wastewaters and with low detection frequencies. The most ubiquitous compounds, present in all influent and effluent wastewater samples analyzed, were the cocaine metabolite benzoylecgonine, and the amphetamine-like compounds ephedrine (EPH) and 3,4-methylenedioxymethamphetamine (MDMA or ecstasy). Cocaine, cocaethylene (CE, transesterification product of cocaine formed after the joint consumption of cocaine and ethanol), and morphine (MOR) were detected in all influent, but not in all effluent wastewaters (see Fig. 2). 

The consumption indicator is the metabolic byproduct excreted at the highest rate. It may be a metabolite, as it is the case for cocaine (BE) and heroin (MOR), or the drug itself, as it is the case of amphetamine-like compounds. THC, the most psychoactive cannabinoid of the cannabis herb, is highly metabolized before excretion, thus, the consumption indicator selected (THC-COOH) presents an excretion rate of 0.6%. Despite the fact that OH-THC presents a slightly higher excretion rate (2%), this analyte was not selected to back calculate cannabis use due... 

The present work reports on the presence of illicit drugs and metabolites in waste and surface waters of the Ebro River basin. In agreement to previous works done in this line in other locations of Spain and in diverse European countries, the most abundant and ubiquitous compounds in waters were cocaine and its major metabolite benzoy-lecgonine, and the amphetamine-like compounds ephedrine and ecstasy. Removal of these compounds during wastewater treatment processes was considered satisfactory for most compounds, but not enough to avoid the presence of these... 

Cocaine-mediated hepatotoxicity has been associated with the conversion of cocaine to norcocaine and further oxidation products. The enzymes involved in in vitro hepatic oxidative N-demethylation of cocaine (192) were investigated (237), and two different enzymatic pathways appear to be important in the formation of the hepatotoxic metabolite. Cytochrome P-450 monooxygenases accomplish the direct N-demethylation of cocaine to norcocaine (194) as confirmed by induction and inhibition studies (Scheme 42). The second pathway for cocaine N-demethylation involves formation of cocaine /V-oxide (193) as an intermediate and two enzymes. A flavin-containing monooxygenase is first thought to convert cocaine to cocaine /V-oxide, followed by cytochrome P-450-... 

Cartmell, L.W., Aufderheide, A.C., Springfield, A., Weems, C. and Arriaza, B. (1991). The frequency and antiquity of Prehistoric coca-leaf-chewing practices in Northern Chile radioimmunoassay of cocaine metabolite in human mummy hair. Latin American Antiquity 2 260-268. 

The standard urine immunoassay for detection of cocaine (23a) abuse during the gestation period of newborn babies was frequently found to yield negative results in cases where positive results were shown by extraction of meconium with a solvent, followed by HPLC. The drug and metabolites such as norcocaine (23b) and cocaethyline (23c) were detected140. See Section IV.C for an alternative analysis of cocaine. 

Table 7.3. Effect of Acute Ethanol Administration on Tissue Concentrations of Cocaine and Its Major Metabolites in the Raf)...

U. A. Boelsterli, C. Goldlin, Biomechanisms of Cocaine-Induced Hepatocyte Injury Mediated by the Formation of Reactive Metabolites , Arch. Toxicol. 1991, 65, 351 — 360. 

Once in the blood stream, cocaine levels quickly rise in the brain, faster than plasma levels, which then redistribute to other tissues. Cocaine is rapidly metabolized in the blood and liver, with a half-life of 30 to 90 minutes. The major metabolites have a half-life of approximately 8 hours. Although cocaine itself is detected in urine for only 12 hours, the metabolite benzoylecgonine can be detected in urine for at least 48 hours and sometimes up to 2 weeks. Concurrent use of cocaine and ethanol produces an ethyl ester of benzoylecgonine called cocaethylene. Cocaethylene is an active metabolite, blocking dopamine reuptake, and potentiating the effect of cocaine. Thus, concurrent use of cocaine and ethanol can further increase the additional effects of the drugs and the risk of dependency. 

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