Isolation and characterization of carbinolamide and phenolic glucuronide conjugates of (+-)-N-methyl-N-(1-methyl-3,3-diphenylpropyl) formamide and N-formylmethamphetamine by FAB/MS, LC/MS/MS, and NMR

Drug Metab Dispos. 1992 May-Jun;20(3):451-60.

Abstract

The metabolic disposition of (+-)-N-methyl-N-(1-methyl-3,3- diphenyl-propyl)formamide, especially with regard to the formation of water soluble glucuronides, is described. The glucuronide conjugates, (+-)-N-hydroxymethyl-N-(1-methyl-3,3-diphenylpropyl)formamide glucuronide, (+-)-N-methyl-N-[1-methyl-3-(4'-hydroxyphenyl)-3-phenylpropyl]formamide glucuronide, and (+-)-N-methyl-N-[1-methyl-3-(4'-hydroxy-3'-methoxyphenyl)-3- phenylpropyl]formamide glucuronide were isolated from the bile of rats dosed with the parent compound. These conjugates were characterized spectroscopically by 1H-NMR, FAB/MS, and LC/MS/MS. Because it is becoming more common to isolate the intact glucuronide conjugates of xenobiotics, we investigated some common mass spectral fragmentation patterns of these conjugates, especially by LC/MS/MS. The fragmentation patterns for each of the conjugates were obtained under MS/MS conditions and compared. Specifically, the fragmentation patterns of phenolic glucuronide and an aliphatic O-glucuronide, in particular a carbinolamide glucuronide, were investigated. The data obtained from these studies was used to predict the nature of glucuronide conjugates obtained from rats dosed with the formamide analog, N-formylmethamphetamine. This is the first spectroscopic characterization of an intact carbinolamide glucuronide conjugate isolated from the bile of rats.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzhydryl Compounds / chemistry*
  • Benzhydryl Compounds / isolation & purification
  • Benzhydryl Compounds / metabolism
  • Bile / chemistry
  • Chromatography, High Pressure Liquid
  • Formamides / chemistry*
  • Formamides / isolation & purification
  • Formamides / metabolism
  • Glucuronates / chemistry*
  • Glucuronates / isolation & purification
  • Glucuronates / metabolism
  • Magnetic Resonance Spectroscopy
  • Male
  • Methamphetamine / analogs & derivatives*
  • Methamphetamine / chemistry
  • Methamphetamine / isolation & purification
  • Methamphetamine / metabolism
  • Rats
  • Rats, Inbred Strains
  • Spectrometry, Mass, Fast Atom Bombardment

Substances

  • Benzhydryl Compounds
  • Formamides
  • Glucuronates
  • N-(1-methyl-3,3-diphenylpropyl)formamide
  • N-formylmethamphetamine
  • Methamphetamine