HIGH-FIELD DEUTERIUM NUCLEAR-MAGNETIC-RESONANCE SPECTROSCOPIC MONITORING OF THE PHARMACOKINETICS OF SELECTIVELY DEUTERATED BENZOIC-ACID IN MAN

被引:11
作者
AKIRA, K
FARRANT, RD
LINDON, JC
CADDICK, ST
NICHOLLS, AW
NICHOLSON, JK
机构
[1] UNIV LONDON BIRKBECK COLL,DEPT CHEM,LONDON WC1H 0PP,ENGLAND
[2] WELLCOME RES LABS,DEPT PHYS SCI,BECKENHAM BR3 3BS,KENT,ENGLAND
关键词
D O I
10.1006/abio.1994.1415
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
The stable isotope tracer technique using C-13 labeling of substrates followed by NMR spectroscopy of biofluids has been widely used in metabolic investigations, whereas the use of H-2 labeling and H-2 NMR spectroscopy has been extremely limited. The applicability of the high-field H-2 NMR spectroscopy (14.1 T, 92 MHz H-2 frequency) in a simple pharmacokinetic problem has now been investigated using selectively deuterated benzoic acid (BA) as a model. [7-C-13,2,6-H-2(2)]BA was synthesized for use as a tracer to compare the efficiency and sensitivity of H-2 and C-13 labeling. The urinary excretion of [7-C-13,2,6-H-2(2)]hippuric acid (HA) formed from orally administered [7-C-13,2,6-H-2(2)]BA (250 mg) was followed by 92-MHz H-2 and 150-MHz C-13 NMR spectroscopy (only 10 min accumulation time) following concentration of urine by a factor of 10, using a standard for quantitation. The heights of resonances for (13)C7 and (2)H2,6 were used to calculate the [7-C-13,2,6-H-2(2)]HA concentration. The lower limit of detection using this H-2 NMR approach was approximately 60 nmol/ml and was found to be comparable with that of the C-13 NMR approach where the quaternary carbon (C7) was labeled. The administered [7-C-13,2,6-H-2(2)]BA was found to be quantitatively biotransformed to HA and excreted in urine within 4 h by both NMR approaches. The H-2 NMR approach using a high-field NMR spectrometer is potentially useful and practical for pharmacokinetic research on small molecules whose H-2 resonances are relatively sharp since the procedures are very simple and convenient. (C) 1994 Academic Press, Inc.
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页码:297 / 302
页数:6
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