Table 2

Aromatic-type quaternary ammonium–linked glucuronide metabolites of drugs identified in human urine

AglyconeQualitative IdentificationQuantitative AnalysisReferences
Reference Standard2-a1H NMR2-b δSoft Ionization MS2-cOther2-dTechnique2-eMean % Dose Excreted in Urine as N+-Glucuronide (N)2-f
Antifungal agents
 TioconazoleNA5.55FABHVE, IND, NOERA10.5  (NG) MacRaeet al., 1990
 LamotrigineNA5.37API, FAB 13C NMR, IND, T MSIND63  (10) Cohen et al., 1987; Sinz and Remmel, 1991b; Remmel and Sinz, 1991
Environmental chemicals
 NicotineOS5.72FABIND1.5 ± 2.1 (4)2-g  (SM) Byrd et al., 1992, 1994; Seatonet al., 1993
 CotinineOS5.82API 13C NMR, 2D NMR, IND, NOEIND17 ± 11 (4)2-g  (SM) Byrd et al.,1992, 1994; Caldwell et al., 1992
Drugs under development
 ImiloxanNA5.53FABEI MSRANG Rush et al., 1992
 LY 108380NANG NDFD MS, INDRA55  (3)(IM) Rubin et al., 1979
 MPTD2-h NA5.77FAB2-i CI MS, IND, UVRA52 ± 10  (4)2-g McKillop et al.,1990
 Nafimidone alcohol2-j NA5.40FABINDHPLC-RA24  (2)2-g Rush et al., 1990
 Cyclized metabolite of oltipraz2-j NA5.64 ND 13C NMR, EI MS, IND, IR, UVNG2-k Beider et al.,1983
 WY-18,2512-l NANGFABINDHPLC-UV4 (2)  (IV) Janssen et al., 1982
  • NA, not available; ND, not determined; NG, data not given.

  • 2-a BS, prepared by biochemical synthesis; OS, prepared by organic synthesis.

  • 2-b Data given for anomeric proton, a doublet in each case.

  • 2-c Molecular cation assigned using API (atmospheric pressure ionization–type technique) or FAB (fast atom bombardment).

  • 2-d CI MS, chemical ionization mass spectrometry; EI MS, electron impact mass spectrometry; FD MS, field-desorption mass spectrometry; HVE, high-voltage electrophoresis; IND, indirect identification by analysis of the aglycone released by β-glucuronidase and/or base treatment; IR, infrared spectroscopy; NOE, NMR nuclear Overhauser enhancement experiments; T MS, tandem mass spectrometry; 2D NMR, two-dimensional NMR techniques; UV, ultraviolet spectroscopy.

  • 2-e IND, indirect quantification by analysis of the aglycone released by β-glucuronidase or base treatment; HPLC-RA, HPLC with a radioactivity monitor; RA, radiometric assay.

  • 2-f Data expressed as mean ± SD (N) and obtained after oral administration (except where stated; IM, intramuscular administration; IV, intravenous administration; SM, cigarette smoking).

  • 2-g Mean percentage of urinary metabolites.

  • 2-h Investigated in baboon.

  • 2-i No molecular cation detected.

  • 2-j After administration of the parent drug.

  • 2-k A major metabolite, but data not given.

  • 2-l Investigated in rhesus monkey.