The IKBFU scientists proposed that instead of traditional complex approaches, they should assess the concentration and chemical composition of drugs using vibrational spectroscopy and nuclear magnetic resonance methods. After analyzing the work of their colleagues, the authors concluded that these methods allow them to obtain accurate results within a few minutes timeframe, while keeping the activity and structure of the molecules intact. In addition, they can be used to detect drugs directly in blood and other human biological fluids. Thanks to this, vibrational spectroscopy and nuclear magnetic resonance will help check the quality of drugs in pharmaceutical production, as well as assess their safety for patients. The results of the study, supported by grants from the Russian Science Foundation and the Russian Foundation for Basic Research, were published in Drug Metabolism and Personalized Therapy Journal.
In order to assess how the drug behaves in the human body, what organs it enters, and how long it circulates in the blood, scientists require special methods to identify chemical substances in biological fluids. To this end, two laboratory approaches are most commonly used in high-performance liquid chromatography and mass spectrometry. These methods allow researchers to identify the drug, its targeted concentration and molecular composition. However, those methods are expensive, time-consuming, and can only be performed by highly trained professionals. In addition, they cannot be used for real-time analysis. Therefore, scientists are looking for new approaches to identify and assess drug concentrations.
Scientists from the university proposed to determine the amount of active ingredient in drugs using the methods of vibrational spectroscopy and nuclear magnetic resonance.
The first approach is based on irradiating the solution with infrared or ultraviolet light, after which a special device picks up the response glow from the compound. The spectrum of the «response» wavelengths differs from substance to substance, so that the chemical composition of the solution can be determined. In addition, the concentrations of the different components in the mixture can be determined from the height of the radiation peaks in the spectra. The advantages of vibrational spectroscopy are that it is a fast and highly sensitive method which does not destroy samples, even if they are living cells.
The nuclear magnetic resonance method also makes it possible to obtain spectra of substances that are part of the mixture under analysis. In this case, the source of radiation is atomic nuclei, which respond in a special way to the action of the magnetic field. In the normal state, they do not manifest themselves in any way, but when placed in a magnetic field they begin to emit electromagnetic waves. Such atoms are found in large numbers in the human body, which is why nuclear magnetic resonance is used in the diagnosis of diseases, as well as in molecules of medicines. Therefore, by the intensity of the signal it is possible to estimate the amount of the active substance.
Researchers analyzed databases of scientific articles, the authors of which determined the concentrations of various drugs using the methods described above. The scientists found that vibrational spectroscopy has been successfully used to detect anti-tumor drugs in the blood of cancer patients. The approach also allowed other groups of researchers to determine levels of aspirin, vitamin C and five different antibiotics in the blood and urine.
In addition, it turns out that based on the vibrational spectroscopy method, Chinese scientists have developed a handheld device that allows them to determine drug concentrations directly in muscles and in blood circulating through blood vessels. This is done in real time using a sensor, a thin needle that is inserted into a vein or muscle.
Analysis of the scientific literature also showed that the prospects of the nuclear magnetic resonance method are not inferior to vibrational spectroscopy. In addition, scientists have demonstrated that nuclear magnetic resonance can detect side effects from treatment, such as the accumulation of toxic substances in the blood.
Vladimir Rafalsky, MD, director of the Immanuel Kant Federal University Clinical Research Center, and Andrey Zyubin, PhD, head of the Laboratory for Mathematical Modeling of Optical Properties of Nanomaterials at the Immanuel Kant Federal University told us about their research:
We estimate both methods to be extremely promising and universally applied in clinical practice. In addition, they can be combined. For example, since both approaches do not destroy the molecules, the same sample can be analyzed multiple times — first by nuclear magnetic resonance and then by spectroscopy. In the future, we will test other combinations of methods for analyzing drug concentrations.