Use of 1H-NMR spectroscopy to determine the enantioselective mechanism of neutral and anionic cyclodextrins in capillary electrophoresis.

One-dimensional (ID) and two-dimensional (2D) 1H nuclear magnetic resonance (NMR) techniques have been used to investigate the chiral recognition process in capillary electrophoresis (CE) for seven different cyclodextrins (CDs) with the calcium channel blocker amlodipine as a model compound. These include five neutral CDs (alpha-CD, beta-CD, gamma-CD, hydroxypropyl-beta-CD and hydroxyethyl-beta-CD) and two anionic CDs (sulphobutyl-ether-beta-CD and carboxymethyl-beta-CD) where mixtures of amlodipine with each of the seven CDs were examined by 1D NMR in deuterated phosphate buffer at pD 3.4. The resonance shift of signals with added CD, relative to the CD-free position (shift displacement, delta delta) and shift non-equivalence (delta delta *) of enantiomeric signals shifted relative to each other after addition of CD were examined for non-overlapped protons of amlodipine. The possible correlations of NMR shift non-equivalence data with chiral separation in CE for amlodipine have been critically assessed. Qualitative differences in the 1D NMR shifts and enhanced enantioselectivity in CE were observed for amlodipine with sulphobutyl-ether-beta-CD. Further experiments on the through-space interactions using 2D rotating frame nuclear Overhauser effect spectroscopy (ROESY) indicated that there was no association between internal glucopyranose hydrogen atoms and the aromatic hydrogens of amlodipine. This gives evidence for the aromatic ring not being included in this CD. Moreover, data from spin-lattice relaxation times (T1) measured for amlodipine in the free state and after addition of the anionic sulphobutyl-ether-beta-CD indicate that the aromatic moiety of amlodipine is not included into the sulphobutyl-ether-beta-CD cavity. There is evidence that it interacts with the sulphobutyl side chains, and may adopt a preferred orientation outside the sulphobutyl-ether-beta-CD toroid itself.

Isolation, characterization and direct estimation of dazoxiben and its glucuronide from human plasma and urine.

1. The major metabolite of dazoxiben in human urine was isolated by XAD-2 and silica chromatography, then identified as a glucuronide conjugate by mass spectrometry and n.m.r. spectroscopy. 2. Levels of dazoxiben and the metabolite in plasma were measured by extraction onto activated charcoal, followed by h.p.l.c. analysis. 3. The method has been used to determine the pharmacokinetics of the drug and metabolite, after intravenous and oral administration of single 100 mg doses to man.

13C-NMR studies on 1-N-[(S)-4-amino-2-hydroxybutyl]kanamycin A (butikacin) and related aminoglycosides.

The 13C-NMR spectra of 1-N-[(S)-4-amino-2-hydroxybutyl]kanamycin A (butikacin) (Fig. 1, 1b) and some of its related compounds have been recorded and are tabulated, assigned and discussed. The chemical shifts of many of the carbon nuclei are shown to be reasonably invariant amongst this series of compounds. A procedure is described for the determination of the (R,S)-epimer ratio of kanamycin A derivatives which have N-substituted groups containing a chiral centre.