Karl Pfleger

Identification and differentiation of benzodiazepines and their metabolites in urine by computerized gas chromatography-mass spectrometry.

A method for the identification and differentiation of the following benzodiazepines and their metabolites in urine after acid hydrolysis and acetylation is described: bromazepam, camazepam, chlordiazepoxide, clobazam, clonazepam, clorazepate, clotiazepam, cloxazolam, delorazepam, diazepam, ethylloflazepate, flunitrazepam, flurazepam, halazepam, ketazolam, loprazolam, lorazepam, lormetazepam, medazepam, metaclazepam, midazolam, nitrazepam, nordazepam, oxazepam, oxazolam, prazepam, quazepam, temazepam and tetrazepam. The acetylated extract was analysed by computerized gas chromatography-mass spectrometry. An on-line computer allowed rapid detection using ion chromatography with ions m/z 205, 211, 230, 241, 245, 249, 312 and 333. The identity of positive signals in the reconstructed ion chromatogram was confirmed by a comparison of the stored full mass spectra with reference spectra. The ion chromatograms, reference mass spectra and gas chromatographic retention indices (on OV-101) are documented.

Identification and differentiation of alkylamine antihistamines and their metabolites in urine by computerized gas chromatography-mass spectrometry.

A gas chromatographic-mass spectrometric screening procedure is described for the identification and differentiation of the following alkylamine antihistamines and their metabolites in urine: azatadine, benzquinamide, brompheniramine, chlorphenamine, (clofedanol), cyproheptadine, dimetindene, ketotifen, mebhydroline, phenindamine, pheniramine, pyrrobutamine, terfenadine and tolpropamine. After acid hydrolysis of the conjugates, extraction and acetylation, the urine samples were analysed by computerized gas chromatography-mass spectrometry. Using ion chromatography with the selective ions m/z 58, 169, 203, 205, 230, 233, 262 and 337, the presence of alkylamine antihistamines and/or their metabolites was indicated. The identity of positive signals in the reconstructed ion chromatograms was confirmed by a visual or computerized comparison of the stored full mass spectra with the reference spectra. The ion chromatograms, reference mass spectra and gas chromatographic retention indices (OV-101) are documented. The procedure presented is integrated in a general screening procedure (general unknown analysis) for several groups of drugs.

Screening procedure for the detection of opioids, other potent analgesics and their metabolites in urine using a computerized gas chromatographic-mass spectrometric technique

ZusammenfassungEine Methode zum Nachweis von Opioiden, anderen starken Analgetica und deren Metabolite im Urin nach saurer Hydrolyse wird beschrieben. Der acetylierte Extrakt wird mit der Kopplung Gas-Chromatographie-Massenspektrometrie-Datenverarbeitung analysiert. Ein online-Computer erlaubt eine rasche Auswertung durch die Verwendung der Massenfragmentographie mit den Massen 58, 72, 87, 299, 327, 341, 343, 371 und 69, 71, 100, 125, 187, 220, 242, 261. Die Verbindungen, die im rekonstruierten Massenfragmentogramm angezeigt werden, können durch Vergleich der zugrunde liegenden Massenspektren mit Referenzspektren identifiziert werden. Das Massenfragmentogramm, die zugrunde liegenden Massenspektren und die gaschromatographischen Retentionsindices (OV 101) werden gezeigt.SummaryA method for detecting opioids, other potent analgesics and their metabolites in urine after acid hydrolysis is described. The acetylated extract is analysed by computerized gas chromatography-mass spectrometry. An online computer allows rapid identification using mass fragmentography with the masses 58, 72, 87, 299, 327, 341, 343, 371 and 69, 71, 100, 125, 187, 220, 242, 261. The identity of positive signals in the reconstructed mass fragmentogram is established by a comparison of the entire mass spectra with those of standards. The mass fragmentogram, the underlying mass spectra and the gas chromatographic retention indices (OV 101) are documented.

Untersuchungen über den oxydativen stoffwechsel des phenacetins bei der ratte

Abstract Following the administration of phenacetin to rats the urinary excretion of phenacetin, N-acetyl-p-aminophenol, n-acetyl-p-aminophenol-sulfate, N-acetyl-p-amiunophenolglucuronide, p-phenetidine, 2-hydroxyphenetidinesulfate and 2-hydroxyphenacetin was measured 3-hydroxyphenacetin was detected as a new metabolite of phenacetin. In vitro, 2-hydroxyphenacetin and 3-hydroxyphenacetin were found in rat liver slices and in the 20,000 g liver fraction as metabolites of phenacetin. Results obtained with p-phenetidine in vitro indicate that the high percentage of 2-hydroxyphenetidine in the overall excretion of phenacetin in vivo is due to the hydroxylation of p-phenetidine and does not result from hydroxylation of phenacetin followed by deacetylation.

Screening procedure for detection of phenothiazine and analogous neuroleptics and their metabolites in urine using a computerized gas chromatographic—mass spectrometric technique

A method for the identification of phenothiazine and analogous neuroleptics and their metabolites in urine after acid hydrolysis is described. The acetylated extract is analysed by computerized gas chromatography-mass spectrometry. An on-line computer allows rapid detection using mass fragmentography with the masses m/e 58, 72, 86, 98, 100, 113, 114, 141 and 132, 148, 154, 191, 198, 199, 243, 267. The identity of positive signals in the reconstructed mass fragmentograms is established by comparison of the stored entire mass spectra with those of standards. The mass fragmentograms, the underlying mass spectra and the gas chromatographic retention indices (OV-101) are documented.

Determination of 1,4- and 1,5-benzodiazepines in urine using a computerized gas chromatographic—mass spectrometric technique☆

A method for the determination of benzodiazepines and their main metabolites in urine after acid hydrolysis is described. The extract is analyzed by computerized gas chromatography-mass spectrometry. An on-line computer allows rapid detection using mass fragmentography with the masses m/e 211, 230, 241, 244, 249, 262, 276, and 285. The mass fragmentogram and the underlying mass spectra of the hydrolysis products (benzophenones and analogues) are documented.

Potenzierung der adenosinwirkung am herzen durch inosin

Abstract In guinea-pigs, inosine potentiated, in vitro as well as in vivo , the negative chronotropic and negative dromotropic action on the heart of adenosine. When administered simulataneously with inosine, adenosine showed in vivo a 6-fold increase of its cardiac action, and a 3-fold increase in vitro . 57% of 14 C-adenosine administered i.v., was taken up by the lungs within 30 sec. Inosine reduced this uptake into the lungs and into other organs. This resulted in an increase in the adenosine concentration of the arterial blood. In the presence of inosine, the 14 C-adenosine concentration of arterial blood was increased 8-fold. About 50% of 14 C-adenosine incubated with guinea-pig blood was deaminated to 14 C-anosine after 60 sec. An estimate of the rate of deamination as compared with the rate of uptake suggested that more than 90 per cent of the adenosine administered was taken up by the organs, whereas the erythrocytes played only a minor role in the inactivation of adenosine.

Ausscheidung freien und konjugierten Sulfates bei Ratte und Menschen nach Verabreichung von N-Acetyl-p-Aminophenol

SummaryIn rats, urinary excretion of free sulfate decreases by 90% following the i.p. administration of 200 mg/kg N-acetyl-p-aminophenol (NAPAP). It seems that the conjugation with sulfuric acid as measured by the excretion of NAPAP-sulfate is limited by the amount of inorganic sulfate available. By addition of sodium sulfate or sodium thiosulfate, the sulfate conjugation can be increased by 100% and, consequently, the excretion of NAPAP is markedly enhanced. After administration of phenobarbital an increase in urinary excretion of NAPAP-sulfate due to induction can be observed if the concentration of sulfate is not limited.In man, too, urinary excretion of free sulfate is diminished after administration of 2 g NAPAP; simultaneously, the excretion of physiological conjugates of sulfate is decreased.ZusammenfassungBei der Ratte nimmt nach i.p. Verabreichung von 200 mg/kg N-Acetyl-p-aminophenol (NAPAP) die Ausscheidung des freien Sulfates im Urin um ca. 90% des Kontrollwertes ab. Demnach ist die Konjugation mit Schwefelsäure bei der Ratte — gemessen an der Ausscheidung von NAPAP-sulfat — durch die verfügbare Menge an anorganischem Sulfat limitiert. Durch Zulage von Natriumsulfat bzw. Natriumthiosulfat wird die Sulfat-Konjugation bis zu 100% erhöht und damit die Elimination des NAPAP insgesamt beträchtlich gesteigert. Nach Phenobarbital-Vorbehandlung und gleichzeitiger Sulfatzulage tritt eine induktiv bedingte Mehrausscheidung an NAPAP-sulfat auf.Auch beim Menschen wird nach Gabe von 2 g N-Acetyl-p-aminophenol bis zu 50% weniger freies Sulfat ausgeschieden. Außerdem wird nach dieser NAPAP-Dosis die Ausscheidung physiologischer Sulfat-Konjugate eingeschränkt.

Mass spectrometry of silylated flavone and flavanone glycosides

Abstract The electron impact mass spectra of 14 trimethylsilylated flavone and flavanone mono- and diglycosides are reported for the first time. All spectra show well defined molecular ion peaks and those of O -glycosides additionally give evidence of the aglycone and the sugar(s), the sugar attachment, the sugar sequence and the interglycosidic linkage (of flavone and flavanone biosides).

Screening procedure for the detection of alkanolamine antihistamines and their metabolites in urine using computerized gas chromatography-mass spectrometry

A gas chromatographic-mass spectrometric screening procedure for the detection of the following alkanolamine antihistamines and their metabolites in urine after acid hydrolysis and acetylation is described: bencyclane, carbinoxamine, chlorbenzoxamine, chlorphenoxamine, clemastine, diphenhydramine, diphenylpyraline, doxylamine, mecloxamine, medrylamine, orphenadrine and phenyltoloxamine. The acetylated extract was analysed by computerized gas chromatography-mass spectrometry. An on-line computer allows rapid detection using ion chromatography with the ions m/z 58, 139, 165, 167, 179, 182, 218 and 260. The identity of positive signals in the reconstructed ion chromatograms was confirmed by a comparison of the stored full mass spectra with the reference spectra. Possible interferences with related compounds that yield the same hydrolysis products or metabolites are discussed. The ion chromatograms, reference mass spectra and gas chromatographic retention indices (OV-101) are documented. The procedure presented is integrated in a general screening procedure (general unknown analysis) for several groups of drugs.