Aromatic-type quaternary ammonium–linked glucuronide metabolites of drugs identified in human urine
| Aglycone | Qualitative Identification | Quantitative Analysis | References | ||||
|---|---|---|---|---|---|---|---|
| Reference Standard2-a | 1H NMR2-b δ | Soft Ionization MS2-c | Other2-d | Technique2-e | Mean % Dose Excreted in Urine as N+-Glucuronide (N)2-f | ||
| Antifungal agents | |||||||
| Tioconazole | NA | 5.55 | FAB | HVE, IND, NOE | RA | 10.5 (NG) | MacRaeet al., 1990 |
| Anticonvulsants | |||||||
| Lamotrigine | NA | 5.37 | API, FAB | 13C NMR, IND, T MS | IND | 63 (10) | Cohen et al., 1987; Sinz and Remmel, 1991b; Remmel and Sinz, 1991 |
| Environmental chemicals | |||||||
| Nicotine | OS | 5.72 | FAB | IND | 1.5 ± 2.1 (4)2-g (SM) | Byrd et al., 1992, 1994; Seatonet al., 1993 | |
| Cotinine | OS | 5.82 | API | 13C NMR, 2D NMR, IND, NOE | IND | 17 ± 11 (4)2-g (SM) | Byrd et al.,1992, 1994; Caldwell et al., 1992 |
| Drugs under development | |||||||
| Imiloxan | NA | 5.53 | FAB | EI MS | RA | NG | Rush et al., 1992 |
| LY 108380 | NA | NG | ND | FD MS, IND | RA | 55 (3)(IM) | Rubin et al., 1979 |
| MPTD2-h | NA | 5.77 | FAB2-i | CI MS, IND, UV | RA | 52 ± 10 (4)2-g | McKillop et al.,1990 |
| Nafimidone alcohol2-j | NA | 5.40 | FAB | IND | HPLC-RA | 24 (2)2-g | Rush et al., 1990 |
| Cyclized metabolite of oltipraz2-j | NA | 5.64 | ND | 13C NMR, EI MS, IND, IR, UV | NG2-k | Beider et al.,1983 | |
| WY-18,2512-l | NA | NG | FAB | IND | HPLC-UV | 4 (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.