Bernd W.K. Diehl,^a Frank Malz^b and Ulrike Holzgrabe^c*
aSpectralservice, Emil-Hoffmann-Str. 33, 50996 Köln, Germany
^bFederal Institute for Materials Research and Testing (BAM), Richard-Willstätter-Str. 11, 12489 Berlin, Germany
^cInstitute of Pharmacy and Food Chemistry, University of Würzburg, Am Hubland, 97074 Würzburg, Germany

Introduction

Quantitative (q) methods in nuclear magnetic resonance (NMR) spectroscopy have been used successfully for many years. However, there is a lack of general acceptance of qNMR in the pharmaceutical industry, whereas chromatographic methods are well established and documented in analytical standards, pharmacopoeia and drug master files.

However, NMR spectroscopy can be considered as a quantitative primary ratio method of measurement, since the ratio of substances in a mixture can be determined directly from the NMR spectral measurement without referencing to another substance. The absolute amount of substances can be determined by using simple reference substances.

The purpose of this short review article is to highlight some capabilities of qNMR spectroscopic methods in drug quality evaluation, indicating that qNMR spectroscopy should be more often applied when chromatographic methods are not working effectively.

NMR spectroscopy can be used in different fields of the quality evaluation of drugs:

• to identify a drug
• to determine the level of impurities and elucidate their structure, and to observe the course of decomposition
• to evaluate the content of residual solvents
• to determine the isomeric composition: the ratio of diastereomers and the enantiomeric excess (ee) by means of chiral additives
• to determine molar ratios of (protonated) basic drugs and (deprotonated) organic acids in respective salts.

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