• Biomolecules & Therapeutics
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• v.4 no.3
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• pp.251-256
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• 1996

The metabolism of carbinoxamine, 2-[(4-chlorophenyl)-2-pyridinyl-methoxy]-N, N-dimethylethaneamine, was studied in adult male volunteers after an oral dose of 15 mg. Solvent extracts of urine obtained with or without enzyme hydrolysis were analyzed by gas chromatography-mass spectrometry after derivatization with MSTFA/TMSCl (N-methyl-N-trimethylsilyltrifluoroacetamide/trimethyl chlorosilane). The structures of metabolites were determined based on the electron impact (EI) and chemical ionization (CI) mass spectra. Nonconjugated metabolites identified in the urine were carbinoxamine, nor-carbinoxamine, and bits-nor-carbinoxamine. Parent drug, nor-carbinoxamine, and bits-nor-carbinoxamine were also detected as conjugated forms. These metabolites observed in human urine were different from those previously reported in the rat. Urinary excretions of carbinoxamine were reached to maxima in 4 hours after drug administration with 4.9%-8.1% and 2.5-4.2% of the dose excreted during 24 h as carbinoxamine and its glucuronide, respectively.

• YAKHAK HOEJI
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• v.37 no.4
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• pp.317-324
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• 1993

The metabolic profile of carbinoxamine, 2-[(4-chlorophenyl)-2-pyridinyi-methoxy] N, N-dimethylethanamine, was determined in rat urine. Urinary extracts obtained with or without enzyme hydrolysis were derivatized with MSTFA/TMSCI (N-methyl-N-trimethylsilyl trifluoroacetamide/Trimethylchlorosilane) and analyzed by GC/MSD. In rat urine, which obtained after oral treatment with carbinoxamine maleate, chlorobenzolyl pyridine, (4-chlorophenyl)-2-pyridinyl methanol : carbinol, 2-[(4-chlorophenyl)-2-pyridinylmethoxy]-N-methylethanamine : norcarbinoxamine, 2-[(4-chlorophenyl)2-pyridinylmethoxy]ethanamine : bis-norcarbinoxamine and parent carbinoxamine were detected in free form. Norcarbinoxamine and bisnorcarbinoxamine were also detected in conjugated form(acetylation). These data suggest that in the rat, hydroxylation of either the benzyl or pyridinyl ring can occur during carbinoxamine elimination. O-demethylation and subsequent conjugation represents the primary pathway of carbinoxamine elimination in the rat.

• Natural Product Sciences
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• v.12 no.1
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• pp.55-61
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• 2006

A description of simple, isocratic and precise reversed phase HPLC methods is given for simultaneous quantification of pholcodine and ephedrine hydrochloride together with either carbinoxamine maleate or terfenadine in antitussive-antihistaminic oral pharmaceutical formulations. Separations were carried out on X-Terra and symmetry shield C18 column $(250\;{\times}\;4.6\;mm,\;5\;{\mu}m)$. The used isocratic elution systems were either $0.02\;M\;KH_2PO_4-acetonitrile$ in the ratio of 75 : 25 and pH adjusted to 7.70 with orthophosphoric acid or sodium hydroxide, for syrup (method A), or 0.02 octanesulphonic acid sodium salt solution-acetonitrile-acetic acid in the ratio of 75 : 25 : 0.5 for suspension (method B). The elution of both mixtures was achieved with a flow rate of 1 ml/min. Detection was carried out by UV absorbance at wavelengths of 220 and 250 nm for syrup and suspension, respectively. The quantification of the components in synthetic mixtures and actual syrup and suspension were calculated using the internal standard technique with metoclopramide HCl and codeine phosphate as internal standards (IS), respectively. The methods, for both mixtures, were validated and met all the requirements for the quality control analysis recommended by FDA and ICH.