The application of absolute quantitative ¹H NMR spectroscopy in drug discovery and development

ABSTRACT

Introduction: The identification of a drug candidate and its structural determination is the most important step in the process of the drug discovery and for this, nuclear magnetic resonance (NMR) is one of the most selective analytical techniques.

Area covered: The present review illustrates the various perspectives of absolute quantitative ¹H NMR spectroscopy in drug discovery and development. It deals with the fundamentals of quantitative NMR (qNMR), the physiochemical properties affecting qNMR, and the latest referencing techniques used for quantification. The precise application of qNMR during various stages of drug discovery and development, namely natural product research, drug quantitation in dosage forms, drug metabolism studies, impurity profiling and solubility measurements is elaborated. To achieve this, the authors explore the literature of NMR in drug discovery and development between 1963 and 2015. It also takes into account several other reviews on the subject.

Expert opinion: qNMR experiments are used for drug discovery and development processes as it is a non-destructive, versatile and robust technique with high intra and interpersonal variability. However, there are several limitations also. qNMR of complex biological samples is incorporated with peak overlap and a low limit of quantification and this can be overcome by using hyphenated chromatographic techniques in addition to NMR.

KEYWORDS:

• ¹H NMR
• absolute quantification
• drug discovery
• drug development

Article highlights

• NMR techniques are the driving force in the discovery of new therapeutic agents through high-throughput screening and structure-based drug discovery.

• The quantitative ¹H NMR technique can be precisely used during various steps of drug formulation and purification purposes.

• NMR based methods are more simple and rapid as compared to other techniques which generally require authentic reference standards for quantification.

• The ¹H NMR methods can be used for providing quick quantitative measurements during API (active pharmaceutical ingredient) development of a drug candidate.

• Recently the expansion of qNMR into the analysis of the metabolome has enabled NMR to contribute to the clinical validation step of drug development.

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Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.