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.

[Discrepant results with immunohistochemical detection TDx/ADx?]. / Diskrepante Ergebnisse bei der immunchemischen Nachweismethode TDx/ADx?

In the last 2 years we had some problems to confirm the thin-layer results (amphetamines, opiates, benzodiazepines, barbiturates and cocaine) with the immunoassay system TDx/ADx. Between January 1989 and December 1990 we did 883 screenings in urine samples (pre- and postmortal) and had 157 discrepancies (20%). In regard of the high level of discrepancies, we had to test the compatibility of TDx and ADx, their detection limits and compared the results with a second method, thin-layer chromatography. Determining the correlation coefficients to prove our results statistically, we found that both systems, TDx and ADx, work reproducible.

[Isolation of chlorphenoxamine metabolites in human urine and their identification]. / Isolierung von Chlorphenoxamin-Metaboliten aus menschlichem Harn und ihre Identifizierung.

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. It cannot be excluded that the compounds VI and VIII are artefacts.

[Cleavage of 2-phenylpropan-1-ol and 2-phenylpropan-2-ol-glucuronide, 2 metabolites of isopropylbenzol (Cumol)]. / Spaltung von 2-Phenylpropan-1-ol-und 2-Phenylpropan-2-ol-Glucuronid, zweier Metaboliten des 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 10.0% HCl, whereby an aglucone yield of nearly 100% is obtained. The second glucuronide behaves otherwise: the recovery of II is very low (only 40% to 45%) with HCl concentrations of 1.0%-20.0%, although with 1.0% HCl 100% of the glucuronide is hydrolysed.

[Cleavage of synthetic pentazocine glucuronide with hydrochloric acid]. / Untersuchungen über die Spaltung von synthetischem Pentazocin-Glucuronid mit Salzsäure.

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). With 5% HCl the rate of hydrolysis only amounted to 40%-43%, whereas I yielded 31% (only 9% was recovered as III). The best III yield was obtained with a HCl concentration of 17.5%.

[Detection and identification of a new metabolite of fenethylline]. / Nachweis und Identifizierung eines neuen Metaboliten des Fenethyllin.

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)]. / Cyanidverluste bei der Aufbewahrung on Blutproben.

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. Blood samples containing no anticoagulant should be homogenized as thoroughly as possible prior to the analysis, e.g. by means of ultrasound treatment.

[Suspected poisoning and actual poisons found in chemico-toxicological emergency investigations (author's transl)]. / Giftverdacht und Giftbefund bei chemisch-toxikologischen Notfalluntersuchungen.

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. In 19% of cases no poison could be demonstrated and in approximately 6% of cases poison ingestion could neither be ascertained nor ruled out. In 53.5% of emergency investigations suspected poisons could be named before the beginning of analysis. The information could be verified partially or completely in 78%. In 20% of these more poisonous substances were found than suspected and in 16.3% none of the suspected substances but completely different toxic ones were demonstrable. In 5.6% of cases suspected poison ingestion could not be verified.

[Isolation and identification of some metabolites of bromazine from human urine (author's transl)]. / Isolierung einiger Metaboliten von Bromazin aus menschlichem Harn and ihre Identifizierung.

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). Another metabolite--extractable at pH 7--was p-hydroxybenzophenone (IX). Treatment of precipitated conjugated compounds with beta-glucuronidase or hydrochloric acid resulted in the liberation of IV, VI and IX, all of which were also found as unconjugated compounds.

[Behaviour of hydroxymethyl-methaqualone-glucuronide in hydrolysis with hydrochloric acid (author's transl)]. / Verhalten von 2'-Hydroxymethylmethaqualon-Glucuronid bei der Spaltung mit Salzsäure.

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. With method III (approx. 5% HCl; 30 min at 100 degrees C) only about 3% of the conjugated compound was converted to the free form.

[Behaviour of p-nitrophenol-glucuronide in hydrolysis with mineral acids (author's transl)]. / Verhalten von p-Nitrophenolglucuronid bei der Spaltung mit Mineralsäuren.

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. No losses were detected, when free p-nitrophenol was treated under the same conditions. Three other methods of hydrolysis have been applied.

[The behaviour of codeine and codeine-6-glucuronide in hydrolysis with hydrochloric acid (author's transl)]. / Verhalten von Codein und Codein-6-glucuronid bei der Hydrolyse mit Salzsäure.

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. The corresponding values: with method II (20% HCl; 6 min heated azeotrope in open vessel) about 8% and with method III (nearly 5% HCl; 30 min at 100 degrees C) about 83%.

[Isolation and identification of some metabolites of clofedanol from human urine (author's transl]. / Isolierung einiger Metaboliten des Clofedanol aus menschlichem Harn und ihre Identifizierung.

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). N,N-dimethylamino-acetic acid (VII) was also identified in urine. Clofedanol and metabolite IV were present as free compounds, and they were also found after hydrolysis of metabolites VIII and IX with beta-glucuronidase.