Normorphine 6-glucuronide

R. T. Brown, N. E. Carter, K. W. Lumbard, and F. Scheinmann, Synthesis of a morphine-6-glucuronide hapten,, V-(4-aminobutyl)normorphine-6-glucuromde, and related haptens, Tetrahedron. Lett., 36 (1995) 8661-8664. 

C. P. W. G. M. Verwey-Van Wissen and P. M. Koopman-Kimenai, Direct determination of codeine, norcodeine, morphine and normorphine with their corresponding O-glucuronide conjugates by HPLC with electrochemical detection, J. Chromatogr., 570 309(1991). 

Heroin is rapidly hydrolyzed in vivo to 6-monoacetylmorphine (257) and thence to morphine (1) (see also p. 26). N-Demethylation and O-demethyla-tion are significant metabolic routes in animals, with the former oxidative process leading to normorphine (258) from 1, and norcodeine (259) from 2, which may in turn be eliminated as their 3- and 6-glucuronides, respectively. 

Normorphine has been found(436) to be excreted as normorphine-3-glucuronide (32%) in dogs. In addition, small amounts of dihydronormorphine (TMS derivative) and 15-dehydronormorphine (TFA derivative) were detected in extracts of dog urine by gc/ms. Dehydration of TV-hydroxy normorphine, not detected during this study, was proposed, tentatively, as the source of the latter. The presence of dihydronormorphine was suspected from the isolation of dihydromorphine as a minor metabolite of morphine/437 ... 

Disposition in the Body. Readily absorbed after oral administration or by injection. Rapidly hydrolysed to 6-monoacetylmorphine in blood and then more slowly metabolised to morphine which is the major active metabolite normorphine is also formed to a minor extent small quantities of codeine are occasionally seen in the urine of addicts, but this is thought to arise from the presence of acetylcodeine as an impurity in illicit heroin samples. All metabolites may be conjugated with glucuronic acid. Up to 80% of a dose is excreted in the urine in 24 hours, mainly as morphine-3-glucuronide with about 5 to 7% of the dose as free morphine, 1% as 6-monoacetylmorphine, 0.1 % as unchanged drug, and trace amounts of other metabolites after inhalation, 14 to 20% of the dose appears in the urine morphine metabolites are excreted in the bile. 

Elimination of heroin (diacetylmorphine) is 80% renal. Metabolic inactivation mainly gives morphine-3-glucuronide together with a few percent of the metabolites 6-monoacetylmorphine, non-conjugated morphine and normorphine. Unchanged diacetylmorphine can be detected only in trace amounts if at all. The hydrolysis of heroin via 3-acetylmorphine takes place to a small extent only [44],... 

After the consumption of morphine, it is rapidly resorbed and distributed in the organism. Up to 90% of the dose is excreted renally within the first 24 h, mainly as glucuronides, and 10% is eliminated via the bile in the feces. Normorphine seldom comprises more than 1% of the amount of substance present in the urine. The percentage of free morphine present increases in parallel with the acidity of the urine [46]. 

Simultaneous acetylcodeine, amphetamine, benzphetamine, benzylmorphine, bromo-STP, buprenorphine, chlorphentermine, codeine, codeine-N-oxide, dextromoramide, dextropro-poxyphene, diamorphine, diethylpropion, dihydrocodeine, dihydromorphine, dimethylam-phetamine, dipipanone, ephedrine, epinephrine, ethoheptazine, ethylmorphine, etorphine, fencamfamin, fenfluramine, fentanyl, hydrocodone, 4-hydroxyamphetamine, levorphanol, mazindol, meperidine, mephentermine, mescaline, methadone, methamphetamine, meth-ylenediojQramphetamine, methylephedrine, monoacetylmorphine, morphine, morphine-3-glucuronide, morphine-N-oxide, naloxone, norcodeine, norlevorphanol, normetanephrine, normethadone, normorphine, norpethidine, norpseudoephedrine, noscapine, o codone, papaverine, pemoline, pentazocine, 2-phenethylamine, phenoperidine, phentermine, phenylephrine, phenylpropanolamine, pholcodeine, pipradol, piritramide, prolintane, pseudoephedrine, STP, thebacon, thebaine, trimethoxyamphetamine, tyramine... 

Heybroek et used PGEs (Ei +0.4 V, E2 +0.9 V vs Pd) in the analysis of codeine and morphine in plasma and gastric juice. Sample preparation was by on-line extraction (ethyl-modified silica column). Codeine-6-glucuronide was measured as codeine after off-line enzymic hydrolysis. Svensson et measured morphine, normorphine and M-6-G as metabolites of codeine using PGEs (Ei +0.25 V, E2 +0.35 V vs Pd) but, because of the low potentials used, the 3-methyl... 

J.-O. Svensson, Determination of morphine, morphine-6-glucuronide and normorphine in plasma and urine with high-performance liquid chromatography and electrochemical detection, J. Chromatogr., 1986, 375, 174—178. 

Isolation and Identification of Morphine 3- and 6-Glucuronides, Morphine 3,6-Diglucuronide, Morphine 3-Etherel Sulfate, Normorphine and Normorphine 6-Glucuronide as Morphine Metabolites in Humans J. Pharm. Sci. 66(9) 1288-1293 (1977) CA 88 4463z... 

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