Oxidation of aliphatic hydroxylamines in aqueous solutions

Beckett, A. H.; Purkaystha, Auditi; Morgan, Philip E.

doi:10.1111/j.2042-7158.1977.tb11230.x

Cited by 21 publications

(5 citation statements)

References 14 publications

(2 reference statements)

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“…As reported above, similar oxidations also took place rapidly when working with C8 columns. In solution, hydroxylamines are generally more stable in acidic conditions, and their aerial oxidation is promoted by neutral or alkaline pH ( , ). Thus, the finding that N -OH-CL easily oxidizes into NO-CL and NO 2 -CL while using C8 columns may be related to the pH (6.8) of the buffer used during this purification step.…”

Section: Discussionmentioning

confidence: 99%

Evidence for a New and Major Metabolic Pathway of Clenbuterol Involving in Vivo Formation of an N-Hydroxyarylamine

Zalko¹,

Debrauwer²,

Bories³

1997

Chem. Res. Toxicol.

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Clenbuterol is a beta-adrenergic agonist widely but illegally used in cattle as a growth promoter. The metabolic fate of this drug remains unknown in the main target species, i.e. the bovine, and only limited data have been published concerning its biotransformations in laboratory animals. A metabolic study has been carried out in the rat using 3H- and 14C-labeled clenbuterol. Urine appeared to be the major excretion pathway. Using a soft technique for urine preparation, extraction, and purification, as well as adequate analytical tools in order to preserve labile metabolites, N-oxidation products of the parental drug on the primary amine function were identified for the first time. Clenbuterol hydroxylamine was the major compound, but 4-nitroclenbuterol was also detected. The metabolic pathway leading to the formation of clenbuterol hydroxylamine prevails at high dosages. Clenbuterol hydroxylamine (but not 4-nitroclenbuterol) was also formed extensively when the drug was incubated with rat liver microsomal fractions in aerobic conditions. It is concluded that oxido reduction during urine preparation have previously impaired the identification of this toxicologically important clenbuterol metabolic route.

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Section: Discussionmentioning

confidence: 99%

Evidence for a New and Major Metabolic Pathway of Clenbuterol Involving in Vivo Formation of an N-Hydroxyarylamine

Zalko¹,

Debrauwer²,

Bories³

1997

Chem. Res. Toxicol.

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“…N ‐Hydroxylamines are readily oxidizable under neutral and alkaline conditions and in the presence of trace metals 116. Primary hydroxylamines degrade to nitroso compounds that equilibrate with the oxime form and secondary hydroxylamines oxidize to the nitrone 117. Zileuton, a lipoxygenase inhibitor, hydrolyzes to an N ‐hydroxylamine intermediate and subsequently oxidizes to the syn‐ and anti‐ N ‐oximes under aqueous and basic conditions (Scheme ) 118…”

Section: Oxidation Of Selected Functional Groupsmentioning

confidence: 99%

Oxidative degradation of pharmaceuticals: Theory, mechanisms and inhibition

Hovorka

Schöneich

2001

Journal of Pharmaceutical Sciences

246

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“…The hydroxylamine intermediate, formed by oxidation of the secondary amine, if present, is rarely observed in vivo for piperazines or other nitrogen-containing alicycles. An explanation for this may be found in reports that this intermediate is inherently unstable (Beckett and Salami, 1972;Beckett et al, 1977;Franklin et al, 1977;Ziegler, 1987); however, identifications of stable alicyclic hydroxylamines have been made (Beckett and al-Sarraj, 1972;Achari and Beckett, 1983;Rodriguez and Acosta, 1997;Zhang et al, 2000). There are even fewer examples of glucuronic acid conjugation of alicyclic hydroxylamines in the literature (Straub et al, 1988;Delbressine et al, 1992;Schaber et al, 2001), and the structures of these metabolites have been largely deduced from mass spectrometry and in some cases 1 H NMR analysis.…”

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confidence: 99%

Identification of a Hydroxylamine Glucuronide Metabolite of an Oral Hypoglycemic Agent

Miller¹,

Doss²,

Stearns³

2004

Drug Metab Dispos

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This article is available online at http://dmd.aspetjournals.org ABSTRACT:Glucuronides of piperazine hydroxylamines are rarely reported in the literature, and even more rarely are their structures unambiguously identified. One major metabolite was detected by liquid chromatography/mass spectrometry-radioactivity in urine from monkeys treated with the aryl piperazine oral hypoglycemic agent 9-[(1S,2R)-2-fluoro-1-methylpropyl]-2-methoxy-6-(1-piperazinyl) purine hydrochloride (1). The mass spectrum of this metabolite indicated that it was both monooxygenated and glucuronidated on the piperazine ring. Possible structures included the N-or O-glucuronic acid conjugates of a carbinolamine, hydroxylamine, or N-oxide. Treatment with ␤-glucuronidase gave a monooxygenated derivative of the parent compound. H NMR analysis of either the glucuronic acid conjugateor the monooxygenated product provided insufficient evidence to unambiguously determine their structures. Incubation of 1 with pig liver microsomes resulted in formation of the same monooxygenated derivative derived from ␤-glucuronidase treatment of the glucuronide metabolite. This in vitro system was used to generate sufficient material for analysis by 13 C NMR, and the metabolite was identified as a hydroxylamine derivative 2. Incubation of the hydroxylamine with monkey liver microsomes and uridine diphospho-5-glucuronic acid gave the same glucuronic acid conjugate as that observed in monkey urine. 13

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Oxidation of aliphatic hydroxylamines in aqueous solutions

Cited by 21 publications

References 14 publications

Evidence for a New and Major Metabolic Pathway of Clenbuterol Involving in Vivo Formation of an N-Hydroxyarylamine

Evidence for a New and Major Metabolic Pathway of Clenbuterol Involving in Vivo Formation of an N-Hydroxyarylamine

Oxidative degradation of pharmaceuticals: Theory, mechanisms and inhibition

Identification of a Hydroxylamine Glucuronide Metabolite of an Oral Hypoglycemic Agent

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