Toxicological detection of ajmaline, prajmaline and their metabolites in urine integrated in a “general-unknown” analysis procedure using gas chromatography-mass spectrometry

Maurer, Hans H.; Pfleger, K.

doi:10.1007/bf00469366

Cited by 6 publications

(3 citation statements)

References 4 publications

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“…Ajrnaline metabolism is rather similar to that of prajmaline (10). The latter is metabolized by monoand di-hydroxylation of the benzene ring and subsequent O-methylation.…”

Section: Urinary Metabolism Of Ajmaline In Poor and Extensive Metabolmentioning

confidence: 78%

Metabolic disposition of ajmaline

Köppel

Tenczer

Arndt

1989

Eur. J. Drug Metab. Pharmacokinet.

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Urine was collected from six patients receiving a continuous infusion of 20 mg/h ajmaline. Pooled urine was extracted with and without enzymatic conjugate cleavage or hydrolysis with concentrated hydrochloric acid. The extracts were analyzed by gas chromatography/mass spectrometry. Ajmaline and its metabolites in urine were identified in the form of their acetylated derivatives. Twenty two different acetylated derivatives of ajmaline and its metabolites could be detected. Three of these derivatives were artifacts generated by acetylation and/or thermal decomposition. The major metabolic pathways were mono- and di-hydroxylation of the benzene ring with subsequent O-methylation, reduction of the C-21, oxidation of the C-17 and C-21-hydroxyl function, N-oxidation, and a combination of these metabolic steps. Ajmaline and its metabolites were mainly excreted in the form of their conjugates. Furthermore, the interference of sparteine, debrisoquine, quinidine, and nifedipine with ajmaline metabolism was studied with semiquantitative thin-layer chromatography. Ajmaline metabolism was inhibited by co-administration of sparteine or quinidine, but not by debrisoquine or nifedipine. Sparteine most likely competed with ajmaline metabolism. Quinidine probably bound competitively to ajmaline-metabolizing enzymes without being metabolized itself. Additionally, the metabolic ratio of hydroxyajmaline/ajmaline in urine was determined in 9 extensive metabolizers and one poor metabolizer of dextromethorphan. The poor metabolizer had a significantly reduced metabolic ratio of hydroxyajmaline/ajmaline, which indicates that ajmaline metabolism probably co-segregates with polymorphic sparteine/debrisoquine/dextromethorphan metabolism.

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“…Ajrnaline metabolism is rather similar to that of prajmaline (10). The latter is metabolized by monoand di-hydroxylation of the benzene ring and subsequent O-methylation.…”

Section: Urinary Metabolism Of Ajmaline In Poor and Extensive Metabolmentioning

confidence: 78%

Metabolic disposition of ajmaline

Köppel

Tenczer

Arndt

1989

Eur. J. Drug Metab. Pharmacokinet.

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“…41 A simpler ion-chromatography method has been described but was not evaluated for anthraquinones. 42 No GC±MS method is routinely available in the UK, although a system is currently being developed and will be displayed on the AssayFinder website under`laxative con®rmation' when available (http://assay®nder. jt2.ox.ac.uk).…”

Section: Gas Chromatography±mass Spectrometrymentioning

confidence: 99%

Screening for surreptitious laxative abuse

Duncan¹

2000

Ann Clin Biochem

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Purgative use, along with blood-letting, has been a mainstay of medical therapy for the last two millennia. Nowadays, prescription laxatives are usually reserved for treating severe constipation or as a bowel washout. 1 However, over-thecounter laxatives are freely available and sold in huge quantities. 2 Chronic laxative use is undoubtedly common and, if excessive, may cause symptoms, the most common being diarrhoea, abdominal pain, general weakness, weight loss, nausea and vomiting. 3 The only sign suggestive

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“…Only about 5% of ajmaline is excreted unchanged with the urine (8). 3 metabolites of ajmaline have been described recently : 10-hydroxyã jmaline, norajmaline, and 21-dihydroajmaline (9). Since oral application does not lead to a reliable antiarrhythmic effect, an extensive first-pass metabolism seems to be likely.…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetics and antiarrhythmic efficacy of intravenous ajmaline in ventricular arrhythmia of acute onset

Köppel

Wagemann

Martens

1989

Eur. J. Drug Metab. Pharmacokinet.

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21 patients with acute myocardial infarction and ventricular arrhythmia of Lown class II-IIIB of acute onset received a short infusion of (50 mg/5 min) ajmaline (Gilurytmal). 6 of the patients had normal kidney and liver function (Group 1), 4 patients had acute renal failure and hemodialysis treatment (Group 2), 4 patients had impaired hepatic function (Group 3), 3 patients had cardiogenic shock (Group 4), and 4 patients had been pretreated with phenobarbital for seizures for at least 5 days (Group 5). A distribution half-life of 6 +/- 1 min and an elimination half-life of 95 +/- 6 min was determined in Group 1. The total plasma clearance was significantly lower in patients with impaired liver or cardiac function and significantly higher in Group 5, whereas impaired renal function did not affect total plasma clearance. After short infusion, ventricular arrhythmia of Lown II-IIIB completely disappeared for at least 16 to 36 min (mean: 19 min), which was associated with an ajmaline plasma level of 0.1-0.45 micrograms/ml. Additionally, steady-state plasma levels of ajmaline were determined after continuous infusion of 10-50 mg/h to 16 patients (Group 6) with ventricular arrhythmia of acute onset (Lown class IVA-V). Ventricular arrhythmia completely disappeared or at least changed to lower Lown classes at ajmaline plasma levels of 0.4-2.0 micrograms/ml. The ajmaline plasma protein binding was 76 +/- 9%. Ajmaline had a special affinity to alpha 1-acid glycoprotein.

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Toxicological detection of ajmaline, prajmaline and their metabolites in urine integrated in a “general-unknown” analysis procedure using gas chromatography-mass spectrometry

Cited by 6 publications

References 4 publications

Metabolic disposition of ajmaline

Metabolic disposition of ajmaline

Screening for surreptitious laxative abuse

Pharmacokinetics and antiarrhythmic efficacy of intravenous ajmaline in ventricular arrhythmia of acute onset

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