INCREASING THE QUANTITATIVE BANDWIDTH OF NMR

Research output: Contribution to conferenceOther

  • External authors:
  • J. Power
  • Mohammadali Foroozandeh
  • R. Adams
  • S. Coombes
  • A.R. Phillips

Abstract

19F NMR is widely used by chemists in the analysis of drugs and their impurities. Typical drugs have only one or two fluorine atoms, but many protons. Thus in comparison to 1H NMR, 19F NMR offers spectra of significantly reduced complexity, simplifying interpretation. Quantitative analysis using 19F, and other nuclei such as 13C that have wide chemical shift ranges, requires constant-phase broadband excitation over the full spectral width. This can be problematic, since due to the limited radiofrequency power available for pulsed excitation, resonance offset effects distort both signal intensities and signal phases. Because only a small spectral width can be excited uniformly using conventional excitation (e.g. a hard 90° pulse), current practice is to make separate measurements for different regions of the fluorine spectrum, using a quantitation standard with an appropriate chemical shift in each case. This is cumbersome and it can be difficult to find appropriate standards. It would be greatly preferable to find a way to achieve quantitative excitation across the full chemical shift range.To compensate for resonance offset effects, composite and/or shaped pulses are commonly used. However, even the best of these methods fall far short of the bandwidths required [1], so swept-frequency “chirp” pulses are needed. In principle, the combination of a 90° and a 180° chirp pulse of appropriate relative amplitude can be used to excite very wide bandwidths [2,3]. Unfortunately, only part of the range excited is usable, because the refocused signal phase still varies in a nonlinear fashion with frequency. A further, hidden, problem is that the signal phase is extremely sensitive to B1 amplitude, so that B1 inhomogeneity causes large (> 30%) losses in signal, even with modern probes. A new broadband sequence, CHORUS (CHirped, ORdered pulses for Ultra-broadband Spectroscopy), has been developed to compensate for this B1¬ sensitivity and to correct the phase errors. CHORUS adds a second 180° chirp pulse, to deliver very uniform, constant-phase excitation over bandwidths of hundreds of kHz, with no undue B1 sensitivity and hence no loss in sensitivity. The accuracies of signal amplitudes and absolute integrals, and their repeatability and robustness, are very satisfactory for quantification purposes; in experimental tests over bandwidths of 100 kHz, drug quantitative analyses showed accuracy and reproducibility better than 1%.Potentially, CHORUS can be a real asset to a range of users, offering much more efficient quantification than simple 90° excitation and allowing a spectrum to be analysed as a whole, with a single standard. For a given RF amplitude, the frequency range over which CHORUS can achieve 98% excitation is about 16 times greater than that for a hard 90° pulse. [1] Odedra S., Thrippleton M. J. and Wimperis S. (2012) J.Magn.Reson, 225, 81-92. [2] Bohlen J. M., Rey M. and Bodenhausen G. (1989) J.Magn.Reson, 84, 191-197. [3] Ermakov V. L., Bohlen J. M. and Bodenhausen G. (1993) J.Magn.Reson. 103, 226-229.

Bibliographical metadata

Original languageEnglish
StatePublished - Sep 2015
EventAstraZeneca Annual review Day - AstraZeneca, Macclesfield

Conference

ConferenceAstraZeneca Annual review Day
CityAstraZeneca, Macclesfield
Period2/09/152/09/15