Title:
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The application of nuclear quadrupole resonance to pharmaceutical analysis
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Research was conducted using nuclear quadrupole resonance (NQR) to investigate its
potential application to pharmaceutical analysis. 14-nitrogen and 35-chlorine quadrupole
resonance frequencies between 1 and 37 MHz have been established and characterised
for a number of materials of pharmaceutical and chemical interest with a view to
applying the technique of NQR to pharmaceutical analysis, possibly on an industrial
scale. Background information and the theory of nuclear quadrupole resonance are
discussed, together with the experimental hardware used, personal instrumental
modifications made, pulse sequences and data processing methods.
The characterisation of materials by other methods currently used in analysis, such as
infrared and X-ray spectroscopy, thermogravimetric analysis and differential scanning
calorimetry, are described and the limits of such techniques compared to those of NQR.
Furosemide, heroin hydrochloride monohydrate, heroin, triazole, histidine, chloroquine
diphosphate, dipicolinic acid and 4-methylimidazole have all been studied and
characterisedto varying degrees with their NQR frequencies, line widths, temperature
coefficients, and relaxation rates having been found experimentally.
The ability to distinguish between polymorphs has been shown in furosemide - an
important consideration in the manufacture of medicines. Quantification using both 14-N
and 35-Cl signalsh as been demonstrated with mass of material being predicted to within
5% in triazole and furosemidc, using free induction decay and pulse-spin locking echo
signals respectively. Quantification of two materials within the same container has been
combined with signal processing techniques in the study of histidine and 4-
methylimidazole. The ability to predict quadrupolar parameters by theoretical calculation
has been shown to be feasible in the case of 14-N nuclei within heroin hydrochloride
monohydratc by modelling. Finally, future perspectives are discussed and the
possibilities and potential of industrial application considered.
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