Characterization of pentoxyverine metabolites in urine using GC/MS after intoxication with Silomat cough drops.

A nearly two and a half year old boy was hospitalized after showing symptoms of disorientation and hallucination. The parents remembered the child playing with a bottle of Silomat cough drops, so that an intoxication was taken into consideration. After liquid/liquid extraction of a urine sample collected in hospital, the underivatized and the acetylated extracts were analyzed by gas chromatography-mass spectrometry (GC/MS) using electron ionization (EI) as well as chemical ionization (CI). In the urine sample high amounts of pentoxyverine (carbetapentane) and several of its metabolites, e.g., different hydrolyzed, desalkylated and ring-hydroxylated products have been identified. The correlation of the results, the observed symptoms, and the access to the Silomat cough drops reveal an intoxication after ingestion of an unknown amount of the antitussive pentoxyverine. Corresponding EI- and CI-GC/MS spectra are presented characterizing the structure of its metabolites.

UHPLC method for the simultaneous determination of ß-blockers, isoflavones and their metabolites in human urine.

A rapid-resolution ultra high-performance liquid chromatography separation method (UHPLC) for the simultaneous determination of the following ß-blockers: milrinone, sotalol, metoprolol, propranolol and carvedilol, and their metabolites: 5'-hydroxylphenyl-carvedilol, O-desmethylcarvedilol, 4-hydroxypropranolol, α-hydroxy-metoprolol, O-desmethyl-metoprolol; the following isoflavones: genistein, daidzein, glycitin, glycitein, puerarin and biochanin A; as well as their metabolites: dihydrogenistein, desmethylglycitein, 8-hydroxygenistein, daidzein-7,4'-diglucoside, 8-hydroxydaidzein, dihydrobiochanin A in human urine was optimized. The analysed compounds were extracted from human urine by means of solid phase extraction (SPE). The effective UHPLC separation of the examined compounds was applied on a Hypersil GOLD™ (50 mm×2.1 mm, 1.9 µm) column with a gradient mobile phase system and a UV detector. The complete separation of all analytes was achieved within 8.0 min. The method was validated for the determination of the aforementioned substances in human urine. The linear ranges, limits of detection (LOD) and limits of quantification (LOQ) for ß-blockers, isoflavones and their metabolites were determined. The intra- and inter-day precision (%C.V.) was less than 4.48%, and the intra-day and inter-day accuracy was less than 4.74%. The tested SPE sorbent proved that appropriate absolute recoveries can be obtained for Oasis HLB (Waters). The mean recovery of the analytes, using the new SPE procedure, amounted from 70.14% to 99.85%. The present paper reports, for the first time, the method for the determination of ß-blockers, isoflavones and their metabolites in human urine samples. The newly developed method was suitably validated and successfully applied for the analysis of the certain of the aforementioned analytes in human urine samples obtained from the patients suffering cardiovascular disease.

Combination of liquid-phase microextraction and on-column stacking for trace analysis of amino alcohols by capillary electrophoresis.

We described a new method for the enrichment of basic drugs present in water samples via liquid-phase microextraction (LPME) combined with on-column stacking in capillary electrophoresis. Two steps were employed to enhance the detection sensitivity of four amino alcohols. The analytes were first extracted from aqueous sample (donor solution) that were adjusted to basic through a thin layer of 1-octanol entrapped within the pores of a polypropylene hollow fiber, and then into a 5-microl acidic acceptor solution inside the hollow fiber. The extract was then further enriched through on-column stacking in capillary electrophoresis. With this two-step enrichment procedure, the method provided 72-110-fold preconcentration of the target amino alcohols. The limits of detection were 0.08-0.5 microg/ml. Relative standard deviation (n=6) ranged between 4.3 and 6.9% for the studied drugs utilizing 2-amino-1-phenylethanol as internal standard. The extraction of amino alcohols in spiked urine samples was evaluated using the developed procedure.

The metabolites of procaterol HCl in urine and faeces of dog and man.

1. The metabolites of procaterol HCl in dog urine and faeces and in human urine were qualitatively analysed by an improved g.l.c.-mass spectrometric method. 2. Trimethylsilylated derivatives of procaterol metabolites were identified by mass fragmentography as procaterol glucuronide, 5-(2-amino-1-hydroxybutyl)-8-hydroxycarbostyril (desisopropylprocaterol), 5-formyl-8-hydroxycarbostyril, 8-hydroxycarbostyril and unchanged procaterol. 3. The metabolic pattern of procaterol HCl was species-independent in rats, dogs and man.

Norephedrines as metabolites of ( 14 C)amphetamine in urine in man.

(+/-)-[(14)C]Amphetamine sulphate (20mg) was administered orally to each of two human male subjects, and 80-85% of the (14)C was excreted in the urine in 2 days. The metabolites in the first day's urine were examined quantitatively. Apart from the metabolites previously described (Dring et al., 1970), norephedrine (2.2 and 2.6% of dose in the two subjects respectively) and 4-hydroxynorephedrine (0.3 and 0.4% of dose in the two subjects respectively) were also found.