Synthesis of the beta-D-glucuronides of 2,3-, 3,4-, and 2,6-dichlorophenol.

The beta-D-glucuronides of 2,3-, 3,4-, and 2,6-dichlorophenol (1-3) were prepared by a modified Koenigs-Knorr synthesis. As the alkaline hydrolysis of perpivaloylated methyl (2,3-dichlorophenyl)-glucuronate 1a led to a dehydrated glucuronide, the preparation of peracetylated methyl dichlorophenylglucuronates with subsequent cleavage of the ester bindings under mild conditions was preferred.

[Isolation of chlorphenoxamine metabolites in human urine and their identification].

After the administration of chlorphenoxamine (2-[1-(4-chlorophenyl)-1-phenylethoxy]-N,N-dimethylethanamine++ +, Systral) (I) the following compounds have been detected in human urine. They were identified as chlorphenoxamine (I), N-demethyl-chlorphenoxamine (II), chlorphenoxamine-N-oxide (III), 1-(4-chlorophenyl)-l-phenylethanol (IV), 1-(4-chlorophenyl)-1-(4'-hydroxyphenyl)-ethanol (V), 1-(4-chlorophenyl)-1-(4'-hydroxyphenyl)-ethene (VI), 1-(4-chlorophenyl)-1-(4'-hydroxy-3'-methoxyphenyl)-ethanol (VII), 1-(4-chlorophenyl)-1-(4'-hydroxy-3'-methoxyphenyl)-ethene (VIII), 2-[1-(4-chlorophenyl)-1-(4'-hydroxyphenyl)-ethoxy]-N-methyl-ethanamine (IX) and 2-[1-(4-chlorophenyl)-1-(4'-hydroxy-3'-methoxyphenyl-ethoxy]- N-methylethanamine (X). The compounds IV, V, VI, VII, VIII, IX and X were also found to be excreted as conjugates.

[Cleavage of 2-phenylpropan-1-ol and 2-phenylpropan-2-ol-glucuronide, 2 metabolites of isopropylbenzol (Cumol)].

The behaviour of 2-phenyl-1-propanol (I) and 2-phenyl-2-propanol (II) and their glucuronides with HCl has been investigated. While I shows a high acidic constancy, II undergoes a partial conversion into 2-phenylpropane (III) which itself yields numerous products. The glucosidic bond of glucuronide I is quantitatively split by 10.

[Cleavage of synthetic pentazocine glucuronide with hydrochloric acid].

It has been reported before that pentazocine (I) and pentazocine-glucuronide (II) form an artifact (III) by the addition of water to the double bond in the presence of HCl. This reaction leads to different results concerning the investigation of the rate of hydrolysis of II and the recovery of I. The glucuronide was quantitatively hydrolyzed by 20% HCl, but yielded only 15% of I (about 64% was detected as III).

[Detection and identification of a new metabolite of fenethylline].

Fenetylline is metabolized in humans on two pathways. In addition to previously described degradation to amphetamine and 7-oxyethyltheophylline fenetylline undergoes moreover oxydative N-dealkylation to yield 7-aminoethyltheophylline and phenylacetone.

[Hydrogen cyanide: losses in samples of stored blood (author's transl)].

Blood samples were mixed with known quantities of KCN and, after various storage times, analysed for the cyanide content. In native blood the losses occurring under the same storage conditions showed an extremely wide variation. In heparinized blood, on the other hand, much better results were obtained.

[Suspected poisoning and actual poisons found in chemico-toxicological emergency investigations (author's transl)].

In almost half (46.5%) of 400 chemico-toxicological investigations suspected poisoning had been assumed without a specific poison being named. In 73% of these cases toxicologically important substances were demonstrated.

[Behaviour of hydroxymethyl-methaqualone-glucuronide in hydrolysis with hydrochloric acid (author's transl)].

The behaviour of the glucuronide derivative of 2'-hydroxymethylmethaqualone with hydrochloric acid was investigated. Three methods of hydrolysis were selected. With method I(12-13% HCl; 30 min at 100 degrees C) about 27% and with method II (20% HCl; 6 min heated azeotrope in open vessel) about 94-95% of the glucuronide derivative was hydrolyzed.

[Isolation and identification of some metabolites of bromazine from human urine (author's transl)].

In addition to the unchanged drug nine metabolites have been found in human urine after the administration of bromazine (2-(p-bromophenyl-phenylmethoxy)-1-N,N-dimethyl-ethylamine). Three compounds were extractable under alkaline conditions; they were identified as bromazine-N-oxide (II), N-monodesmethylbromazine (III) and N-didesmethylbromazine (IV). Two other substances were extractable under alkaline and acidic conditions, p-bromobenzhydrol (VI) and p-bromobenzophenone (VIII).

[Behaviour of p-nitrophenol-glucuronide in hydrolysis with mineral acids (author's transl)].

The behaviour of p-nitrophenol and synthetic p-nitrophenol-glucuronide with mineral acids has been investigated. With sulfuric acid (33%) about 93% of the glucuronide derivative have been hydrolysed; the solution was heated in open vessel for 15 sec. With hydrochloric acid (6%) only about 65% of the conjugated p-nitrophenol have been converted to the free form.

[The behaviour of codeine and codeine-6-glucuronide in hydrolysis with hydrochloric acid (author's transl)].

The behaviour of codeine and codeine-6-glucuronide with hydrochloric acid has been investigated. Three methods of hydrolysis were selected; they are often used in routine identification of drugs in urine. With method I (12--13% HCl; 30 min at 100 degrees C) about 53% of codeine-6-glucuronide were not hydrolized.

[Isolation and identification of some metabolites of clofedanol from human urine (author's transl].

10 excretory products of Clofedanol (1-(o-chlorphenyl)-1-phenyl-3-dimethylaminopropanol) were identified in human urine. The following five products were extracted with chloroform at pH 1--2: o-(chlorphenyl)-phenylmethane (I), benzophenone (II), o-chlorbenzophenone (III), benzhydrol (IV), and o-(chlorphenyl)-beta-phenylacrolein (V). Two compounds were extracted with chloroform at pH 13--14: unchanged Clofedanol and 1-(o-chlorphenyl)-1-phenyl-3-dimethylaminopropene-1 (VI).

[Isolation and identification of some metabolites of phenyramidol (Cabral) from human urine (author's transl)].

The biological transformation of phenyramidol (I), some of which is also excreted unchanged, occurs by three main degradative pathways: 1. Hydroxylation of the pyridine ring in position 3 (metabolite V) and 5 (metabolite VI). 2.

[Isolation and identification of some metabolites of mephenoxalone (Control-OM) from human urine (author's transl)].

Mephenoxalone (5-(o-methoxyphenoxymethyl)-2-oxazolidone) is degraded by various routes in the human, and some is excreted unchanged. In the metabolism of mephenoxalone, the phenoxymethyl ether bond is cleaved; thus o-methoxyphenol (metabolite I) was identified in urine, and 3-amino-1,2-propanediol (IIa) was found after alkaline hydrolysis. Hydroxylation of the benzene ring produces a phenolic hydroxymephenoxalone (metabolite III), and demethylation converts mephenoxalone into demethylmepheonxalone (metabolite IV).

[Quantitative determination of pemoline in serum and urine after ingestion of therapeutic doses (author's transl)].

Serum and urine 5-phenyl-2-imino-4-oxazolidone (pemoline, Tradon) levels have been determined in normal subjects after therapeutic doses (40 mg). Peak levels in serum were reached within 4-6 h (1.1-1.