ReviewNMR techniques in biomedical and pharmaceutical analysis
Introduction
Nowadays, about 65 years after the observation of proton nuclear magnetic resonance (1H NMR) in liquid water and paraffin wax respectively by research groups led by Bloch at Stanford University and Purcell at Harvard University [1], [2], [3], NMR spectroscopy is the preeminent method for determining the structures of synthesized and natural compounds, including the three-dimensional structures of proteins and other macromolecules in solution. However, NMR has also found many applications in other fields than chemistry, such as food science, biology, pharmacy and medicine since it is the only physical method used routinely that can provide quantitative valuable information at the molecular level, regarding analysis of complex mixtures from fluids of biological origin, food materials, beverages, drugs, cell or tissue extracts, excised tissues, cell pellets (in vitro studies) to isolated perfused biological systems (cell or organs) (ex vivo studies) [4], [5], [6], [7], [8], [9], [10], [11], [12], [13], [14], [15] and finally intact living systems (bacteria, plants, animals and humans) (in vivo studies) [16], [17], [18], [19], [20].
Consequently, NMR is unique in its ability to perform analyses in the field of biomedical and pharmaceutical research. This article will focus on the description of some of the NMR techniques used in these domains and their applications. The first part presents an overview of the advantages and limitations of NMR for in vitro quantitative analysis of complex matrices in liquid or semi-solid phases. The second part deals with the NMR-based metabolomics methodology. The third part describes the in vivo clinical magnetic resonance spectroscopy techniques. The fourth part reports some examples of NMR applications in the biomedical and pharmaceutical research fields.
Section snippets
Advantages and limitations of NMR for in vitro quantitative analysis of complex mixtures
NMR is non-invasive and non-destructive so that the sample is available for subsequent analysis by an alternative technique. NMR enables the direct study of intact biofluids and semi-solid or solid samples (e.g. intact cells or tissues, drugs) using magic-angle spinning (MAS) methodology. As solids give generally broad lines, conventional high-resolution NMR is a liquid-phase based technique with signal width lines at half-height usually of a few Hz. However, with the development of high
NMR-based metabolomics
Since the pioneering work of Nicholson et al. [49], there has been an explosive growth in the application of metabolomics. Metabolomics or metabonomics, the two terms being often used interchangeably [50], is a field of study that attempts to detect all the low molecular weight organic metabolites in biofluids, cells, tissues or whole organisms, and applies chemometric methods to identify their key, but potentially subtle changes, as consequence of multiple context-dependent factors including
In vivo magnetic resonance spectroscopy (MRS) techniques
In the context of human (and by extension animal) in vivo studies, NMR spectroscopy is commonly referred to as MRS to avoid the upsetting word “nuclear” when talking to human volunteers or patients as it may erroneously lead to associations with radioactive materials and/or ionizing radiation and also because the technique involves the use of the same scanners than those employed to carry out magnetic resonance imaging (MRI) investigations.
A number of magnetically active nuclei found in
MRS/NMR applications in the biomedical field
We elected to focus our examples to the application of MRS and NMR to brain tumor studies because there is a large body of work that has concentrated on these tumors. For more general applications, the reader can consult for instance the excellent and recent reviews of Soares and Law [99], van der Graaf [86] and DeFeo and Cheng [100].
There are two types of brain tumors: primary brain tumors that originate in the brain and metastatic (secondary) brain tumors that originate from cancer cells that
Conclusion
This article has described the various abilities of NMR spectroscopy in the field of biomedical and pharmaceutical research. Mostly used at its beginning by chemists as a tool for structural elucidation, it has spread to Biochemistry, Pharmacy and Medicine among other disciplines. This is due to its unique properties that are largely discussed here. The versatility of NMR has enabled the technique to make significant and valuable contributions to both the in vitro analysis of complex mixtures
References (150)
- et al.
High resolution proton magnetic resonance spectroscopy of biological fluids
Prog. NMR Spectrosc.
(1989) - et al.
Magnetic resonance spectroscopy: a powerful tool for drug metabolism studies
Biochimie
(1992) - et al.
Theoretical and practical aspects of NMR studies of cells
Immunomethods
(1994) - et al.
NMR spectroscopy of biofluids
- et al.
Fluorine-19 or phosphorus-31 NMR spectroscopy: a suitable analytical technique for quantitative in vitro metabolic studies of fluorinated or phosphorylated drugs
J. Pharm. Biomed. Anal.
(2005) Quantitative NMR spectroscopy in pharmaceutical applications
Progr. NMR Spectrosc.
(2010)- et al.
NMR and plant metabolism
Curr. Opin. Plant Biol.
(2001) - et al.
Overview on sugar metabolism and its control in Lactococcus lactis – the input from in vivo NMR
FEMS Microbiol. Rev.
(2005) Quantitative NMR in the solution state NMR
- et al.
The role of solvents in the signal separation for quantitative 1H NMR spectroscopy
J. Pharm. Biomed. Anal.
(2010)
Optimized metabolite extraction from blood serum for 1H nuclear magnetic resonance spectroscopy
Anal. Biochem.
Microcoil Nuclear Magnetic Resonance spectroscopy
High-throughput tissue extraction protocol for NMR- and MS-based metabolomics
Anal. Biochem.
Analytical technologies for metabonomics and metabolomics, and multi-omic information recovery
Trends Anal. Chem.
In vivo proton MR spectroscopy of the human brain
Progr. NMR Spectrosc.
WET, a T1- and B1-insensitive water-suppression method for in vivo localized 1H NMR spectroscopy
J. Magn. Reson. B
Spectroscopic imaging: basic principles
Eur. J. Radiol.
Magn. Reson. Mater. Phys.
Magnetic resonance spectroscopy of the brain: review of metabolites and clinical applications
Clin. Radiol.
Resonance absorption by nuclear magnetic moments in a solid
Phys. Rev.
Nuclear induction
Phys. Rev.
The nuclear induction experiment
Phys. Rev.
Application of NMR to studies of tissue metabolism
Annu. Rev. Biophys. Biophys. Chem.
Direct 19F NMR spectroscopic observation of 5-fluorouracil metabolism in the isolated perfused mouse liver model
NMR Biomed.
The application of NMR and MS methods for detection of adulteration of wine, fruit juices and olive oil. A review
Anal. Bioanal. Chem.
High-resolution magic-angle-spinning NMR spectroscopy for metabolic profiling of intact tissues
Nat. Protoc.
pH optimization for a reliable quantification of brain tumor cell and tissue extracts with 1H NMR: focus on choline-containing compounds and taurine
Anal. Bioanal. Chem.
Quality control of herbal medicines assessed by NMR
Curr. Pharm. Anal.
MR spectroscopy in clinical research
Acta Radiol.
Proton MR spectroscopy in clinical routine
J. Magn. Reson. Imaging
Noninvasive in vivo small animal MRI and MRS: basic experimental procedures
J. Vis. Exp.
Comparisons of brain metabolites observed by HRMAS 1H NMR of intact tissues and solution 1H NMR of tissue extracts in SIV-infected macaques
NMR Biomed.
Measurement of absolute metabolite concentrations in biological samples
Bruker Rep.
Quantitative analysis of peptides with NMR spectroscopy
Appl. Spectrosc.
Assay by nuclear magnetic resonance spectroscopy: quantification limits
Analyst
Quantitative 1H NMR: development and potential of a method for natural products analysis
J. Nat. Prod.
An algorithm for the automated quantitation of metabolites in in vitro NMR signals
Magn. Reson. Med.
1H HR-MAS and genomic analysis of human tumor biopsies discriminate between high and low grade astrocytomas
NMR Biomed.
Metabolomics in pharmaceutical research and development: metabolites, mechanisms and pathways
Curr. Opin. Drug Discov. Dev.
Comparison of HR MAS MR spectroscopic profiles of breast cancer tissue with clinical parameters
NMR Biomed.
Melanoma tumors acquire a new phospholipid metabolism phenotype under cystemustine as revealed by High-Resolution Magic Angle Spinning Proton Nuclear Magnetic Resonance spectroscopy of intact tumor samples
Cancer Res.
Quantification of choline- and ethanolamine-containing metabolites in human prostate tissues using 1H HR-MAS total correlation spectroscopy
Magn. Reson. Med.
Molecular classification of brain tumor biopsies using solid-state magic angle spinning proton magnetic resonance spectroscopy and robust classifiers
Int. J. Oncol.
Quantitative two-dimensional HRMAS 1H-NMR spectroscopy-based metabolite profiling of human cancer cell lines and response to chemotherapy
Magn. Reson. Med.
Metabolomics of cancer
Methods Mol. Biol. Tumor Biomark. Discov.
Combination of high-resolution magic angle spinning proton magnetic resonance spectroscopy and microscale genomics to type brain tumor biopsies
Int. J. Mol. Med.
Evaluation of lactate and alanine as metabolic biomarkers of prostate cancer using 1H HR-MAS spectroscopy of biopsy tissues
Magn. Reson. Med.
Determination of metabolite concentrations in human brain tumour biopsy samples using HR-MAS and ERETIC measurements
NMR Biomed.
Evaluation of the ERETIC method as an improved quantitative reference for 1H HR-MAS spectroscopy of prostate tissue
Magn. Res. Med.
Quantification of metabolites in breast cancer patients with different clinical prognosis using HR MAS MR spectroscopy
NMR Biomed.
Cited by (106)
Flow-NMR as a Process-Monitoring Tool for mRNA IVT Reaction
2024, Journal of Pharmaceutical SciencesDetermination of drug release profile of doxorubicin encapsulated in SLN with NMR spectroscopy
2022, Journal of Molecular StructurePerformance indicators for a holistic evaluation of catalyst-based degradation—A case study of selected pharmaceuticals and personal care products (PPCPs)
2021, Journal of Hazardous MaterialsCitation Excerpt :The routinely applied nuclei for the measurement of PPCPs mixtures include 1H, 13C, 19F, and 31P (Gladden et al., 2012; Malet-Martino and Holzgrabe, 2011; Zivkovic et al., 2017). Among them, 1H is the most sensitive one for monitoring the reaction process (Malet-Martino and Holzgrabe, 2011). UV–vis spectroscopy is also applied to determine the concentration of target compounds due to its simple operation and less measurement time.
NMR studies of materials loaded into porous-wall hollow glass microspheres
2020, Materials Science and Engineering C