Since the discovery of nuclear magnetic resonance spectroscopy in 1945, the application of NMR in quantitative analysis has been limited for a long time because of the large amount of samples needed and the low sensitivity. It has been only used as the main tool for structural determination for a long time. In the past two decades, NMR has gradually become a powerful quantitative analysis tool due to the rapid development of instruments and the active research of researchers in the field of nuclear magnetic resonance.

Compared with other analytical methods, quantitative NMR analysis has at least the following five advantages:
(1) for a certain nucleus (proton), its signal intensity is directly proportional to the number of nuclei (protons) that produce the signal, but has nothing to do with the chemical properties of the nucleus (proton).
(2) When analyzing a compound in the mixture by internal standard method or relative measurement method, the pure product of the compound is not needed as the reference standard.
(3) The width of the signal peak is very narrow, which is far less than the difference of chemical shifts between the signals, so there is little overlap between the signals of different components in the mixture.
(4) There is no need for molar absorption.

In vivo drug analysis
NMR technology has more outstanding advantages than other conventional methods in the analysis of drugs in vivo: (1) it is easy to operate and does not need complicated extraction or derivatization of samples, which reduces the error. (2) it is non-destructive, and limited biological samples can still be used for other applications after analysis. (3) it can detect drugs and its multiple metabolites under the same physical conditions. (4) it can also be used for other applications after analysis of limited biological samples. (5) The overall biological system can be dynamically monitored to realize the in vivo analysis of drugs. However, some problems, such as low sensitivity, are encountered when NMR technology is introduced into drug analysis in vivo. In addition, the main component of body fluid is water, so it is difficult to detect the signal when using 'H-NMR because the concentration of water proton is much higher than that of the substance to be measured. The currently widely used method of suppressing water peaks is the pre-saturation technique. In addition, methods such as pulsed gradient fields and adding chemicals to enhance the spin-spin relaxation time of water are better methods. Another problem is the interference of endogenous substances. Sometimes when approaching the detection limit, the peaks of hundreds of compounds may appear in the H-NMR. They overlap and interfere with each other, causing difficulties in analysis. This problem can be solved by using a high-resolution nuclear magnetic resonance instrument, or solid phase extraction can be used to first separate the endogenous substances in the biological sample, and then use the NMR instrument for detection. An outstanding feature of the SPE-NMR combined technology is the enrichment of the sample, which can solve the problem of low drug concentration in body fluids, and the cost is relatively cheap.

The application of NMR technology in the quantitative analysis of drugs has many incomparable advantages compared with conventional methods, and it is particularly significant in distinguishing very close drug structures. However, compared with conventional analytical methods, it still has the problems of high detection limit and poor reproducibility. However, it can be predicted that the advantages of this technology will make it increasingly widely used in the quantitative analysis of drugs. With the continuous improvement of technology and the continuous development and popularization of instruments and devices, the technology is likely to become a conventional method for drug quality control.

Author's Bio: 

Creative Biostructure is an innovative biotechnology company founded in 2005, which can help with routine quality control, compound identification, quantitative analysis and assignment along with a wide variety of advance experiments.