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Biomedical subjects

K K Midha

Publications and source records attributed to K K Midha.

240 records · Page 14Linked to original sources
PubMedDate not supplied

The metabolism of p-methoxyamphetamine in dog and monkey. O-demethylation as a major route.

p-Hydroxyamphetamine (PHA) and p-hydroxybenzoic acid (PHBA) have been isolated by gas-liquid chromatography (GC) as urinary metabolites of p-methoxyamphetamine (PMA) in dogs and rhesus monkeys. The amounts of PMA excreted unchanged in the total 24-hr urine samples in dogs and monkeys were 26% and 3%, respectively, of the total administered doses. The amounts of the pharmacologically active metabolite PHA excreted in 24-hr urine samples were 13% in the dog and 44% in the monkey. In the dog, 72% of the PHA was present as free (unconjugated) PHA, whereas in the monkey the amount of PHA present in the free form was only 14%.

Amphetamines↗
PubMedDate not supplied

The identification of urinary metabolites of doxepin in patients.

The metabolism of doxepin was investigated in three patients who provided cumulative urine samples on each of 3 successive days. These samples were examined by means of stereoselective HPLC or HPLC combined with mass spectrometry through a plasmaspray interface (LCMS). In addition, sufficient quantities of the major metabolites were isolated from the urine by column chromatography. The isolated metabolites were examined by HPLC, proton nuclear magnetic resonance spectroscopy (1H-NMR), and chemical ionization and/or electron impact mass spectrometry (EIMS). The resultant spectra and chromatographic properties were compared with authentic reference standards. The metabolites were identified as (E)-2-hydroxydoxepin, (E)-2-hydroxy-N-desmethyldoxepin, (Z)- and (E)-N-desmethyldoxepin, and (Z)- and (E)-doxepin N-oxide. There was no evidence of hydroxylation at the oxymethylene bridge. A further metabolite previously unreported was tentatively identified by LCMS and EIMS as an aromatic hydroxy-N-desmethyldoxepin hydrated at the exocyclic double bond. This metabolite was present in very low amounts, precluding its analysis by 1H-NMR. Moreover, this type of compound dehydrated readily in vitro, and numerous attempts to synthesize reference materials were unsuccessful. The tentative identification of this hydrated metabolite lends significant support to a possible mechanism responsible for the enrichment of cis-N-desmethyldoxepin over time in plasma.

Aged↗
PubMedDate not supplied

alpha-Methyldopamine, a key intermediate in the metabolic disposition of 3,4-methylenedioxyamphetamine in vivo in dog and monkey.

Metabolites of 3,4-methylenedioxyamphetamine in the urine of dogs and monkeys were separated by gas-liquid chromatography as their trifluoroacetyl and/or n-butyl ether derivatives and identified by comparison of the chromatographic and mass spectrometric behavior of these derivatives with those of synthetic compounds. The metabolites identified in dog and monkey urine were alpha-methyldopamine, 3-O-methyl-alpha-methyldopamine, and 3,4-dihydroxybenzyl methyl ketone. The monkey urine also contained 3,4-methylenedioxybenzyl methyl ketone and 3,4-methylenedioxybenzoic acid present as a glucuronide and/or sulfate conjugate, whereas the dog urine had 3-methoxy-4-hydroxybenzoic acid present as a conjugate other than glucuronide and sulfate. The phenolic metabolites in both species were present free and as glucuronide and/or sulfate conjugates.

3,4-Methylenedioxyamphetamine↗
PubMedDate not supplied

3-O-methyl-alpha-methyldopamine, a urinary metabolite of p-methoxyamphetamine in dog and monkey.

Metabolites of p-methoxyamphetamine in the urine of dogs and monkeys were separated by gas-liquid chromatography as their trifluoroacetyl derivatives, and identified by comparison of the chromatographic and mass spectrometric behavior of these derivatives with those of authentic synthetic compounds. The three new metabolites identified in both dogs and monkeys were 3-O-methyl-alpha-methyldopamine, 4-hydroxy-3-methoxybenzyl methyl ketone, and 4-hydroxybenzyl methyl ketone. A fourth new metabolite was tentatively identified in the absence of the appropriate reference standard.

Amphetamines↗