What Is the Role of Spectroscopy in Pharmacokinetics?

By Samudrapom DamReviewed by Lexie CornerNov 1 2024

Pharmacokinetics explores the body's interaction with administered substances/drugs for the entire duration of exposure. This field examines four key parameters: drug absorption, distribution, metabolism, and excretion (ADME).¹

Image Credit: S. Singha/Shutterstock.com

Spectroscopy encompasses various techniques that analyze light’s interaction with matter, providing information on the molecular composition of substances.² In pharmacokinetics, numerous spectroscopic methods are used to study ADME processes.

This article examines the role of different spectroscopy techniques in pharmacokinetics and their impact on drug development.

Spectroscopy Techniques

Ultraviolet-visible (UV-vis) spectroscopy, infrared (IR) spectroscopy, NMR spectroscopy, and mass spectrometry are the common spectroscopy methods used in pharmacokinetics.^3-6

• UV-Vis Spectroscopy has emerged as an effective analytical tool with diverse applications in bio-allied and pharmaceutical sciences. This method relies on the interaction of chemical species with light in the visible and ultraviolet ranges of the spectrum.³
• IR Spectroscopy is a widely used technique that measures the absorption of various infrared frequencies by a sample placed in the path of an IR beam. The purpose of IR spectroscopic analysis is to identify the sample's chemical functional groups, as different groups absorb specific IR frequencies. This makes IR spectroscopy a valuable tool for compound identification and structural analysis.⁴
• NMR Spectroscopy is a noninvasive, nondestructive technique that utilizes the magnetic properties of atomic nuclei to analyze the chemical environment within a molecule. NMR can be applied to both solid and liquid samples in one-dimensional (1D), two-dimensional (2D), and multidimensional (nD) experiments, offering insights into the dynamics, molecular weight, purity, composition, structure, and diffusion properties of nanomaterials.⁵
• Mass Spectrometry is an analytical technique used to measure the mass-to-charge ratio (m/z) of molecules within a sample. This data allows for the calculation of the exact molecular weight of sample components. Mass spectrometers are commonly employed to quantify known compounds, identify unknown compounds by determining molecular weight, and analyze the structure and chemical properties of molecules.⁶

Learn More: The Different Types of Spectroscopy for Chemical Analysis

Spectroscopy Applications in Pharmacokinetics

Drug Discovery

The drug discovery process includes steps like hit identification and confirmation, hit-to-lead progression, and lead optimization. The optimized lead is then advanced to a preclinical candidate (PDC).

Spectroscopy techniques are used to characterize potential drug candidates and their interactions.⁷

For instance, solution NMR spectroscopy provides insights into molecular structures, dynamics, and interactions at the atomic level, making it applicable at multiple steps in target-based drug discovery processes. Ligand-observed NMR experiments are used in screening, while protein-observed experiments help determine ligand binding modes.⁷

Protein labeling with isotopes or modification with NMR-active nuclei is essential in protein-observed experiments for drug discovery. Both protein-based and ligand-based experiments can be used to confirm target–ligand interactions. Solution NMR spectroscopy can also be used in target engagement to probe ligand and protein interactions in living cells.⁷

Preclinical Development

Preclinical development focuses on assessing drug stability and metabolic pathways.^8,9, With drug discovery programs becoming more extended, there is a growing demand for cost-effective, high-throughput, and accurate non-traditional preclinical tools.⁸

Fourier transform infrared micro-spectroscopy (FTIRM) provides an operational platform for this strategic approach, enabling label-free, non-destructive analysis that supports subsequent histological reporting.⁸

FTIRM generates a unique fingerprint spectrum reflecting the global biochemical composition of major cellular macromolecules, either from a cell population or at the single-cell level. IR spectral data from drug-treated cells can provide insights into drug-cell interactions and assess drug efficacy.⁸

IR signal changes can detect cellular alterations even before visible morphological changes appear, providing data valuable for drug screening applications.⁸

Studying drug metabolism is essential for optimizing lead compounds to achieve ideal pharmacokinetic and pharmacodynamic profiles. Techniques such as NMR spectroscopy and mass spectrometry are commonly used to assess the metabolism of a new drug during preclinical safety evaluations.⁹

Clinical Trials

Clinical trials monitor drug concentration in biological samples to evaluate safety and efficacy. UV-Vis spectroscopy is often combined with chromatography methods as a detection tool to identify pharmaceutical compounds and drugs.¹⁰

Similarly, surface-enhanced Raman scattering (SERS) is employed to detect drugs with adequate selectivity and sensitivity, compensating for the typically weak Raman scattering signals. Raman spectroscopy is also applied in clinical research to monitor, analyze, and characterize pharmaceutical drugs in clinical research.¹⁰

NMR spectroscopy provides detailed chemical structure information without damaging samples and is valuable for metabolite determination. For example, it has been used to identify lipoproteins and their metabolites in serum and human plasma.¹⁰

Post-Market Surveillance

Post-market surveillance is a critical tool for correlating a drug's potency with associated adverse events, providing insights into potential positive or negative effects over long-term use. Advances in analytical techniques, such as mass spectrometry and NMR spectroscopy, have enhanced the sensitivity and accuracy of post-market monitoring.^11,12

Pharmaceutical Spectroscopy in Industry

Key providers in pharmaceutical spectroscopy include PG Instruments, Gerstel, Thermo Fisher Scientific, and Agilent Technologies, each offering specialized tools for analytical needs.

PG Instruments supplies UV-Vis and IR spectrophotometers, while Gerstel focuses on chromatography systems integrated with mass spectrometry for thorough drug analysis. Thermo Fisher Scientific and Agilent Technologies provide mass spectrometers and various chromatography and spectroscopy equipment widely used in pharmacokinetics and drug research.

For NMR systems, Magritek and Oxford Instruments provide compact and benchtop options suited for pharmaceutical development and drug discovery applications.

Conclusion

Spectroscopy is essential in pharmacokinetics, enabling detailed analysis of drug interactions and behaviors throughout the drug development process. Techniques like NMR, mass spectrometry, and UV-Vis spectroscopy deepen understanding of ADME processes, supporting phases from drug discovery to preclinical development, clinical trials, and post-market surveillance.

Future advancements in spectroscopy promise to further enhance drug development, reinforcing its vital role in the pharmaceutical industry.

For More: Innovative Protein Structural Analysis with Microfluidic Modulation Spectroscopy

References and Further Reading

1. Grogan, S., Preuss, CV. (2023) Pharmacokinetics. [Online] National Center for Biotechnology Information. Available at https://www.ncbi.nlm.nih.gov/books/NBK557744/ (Accessed on 22 October 2024)
2. Lim, KF. (2022). Spectroscopy: Basic Principles. Encyclopedia of Forensic Sciences, Third Edition (Third Edition). DOI: 10.1016/B978-0-12-823677-2.00033-7, https://www.sciencedirect.com/science/article/abs/pii/B9780128236772000337
3. Singhal, A., Saini, U., Chopra, B., Dhingra, AK., Jain, A., Chaudhary, J. (2024). UV-Visible Spectroscopy: A Review on its Pharmaceutical and Bio-allied Sciences Applications. Current Pharmaceutical Analysis. DOI: 10.2174/0115734129300562240408042614, https://www.ingentaconnect.com/content/ben/cpa/2024/00000020/00000003/art00002
4. Sherman, CP. Infrared Spectroscopy. [Online] Mallinckrodt, Inc. Available at https://mmrc.caltech.edu/FTIR/Literature/General/IR%20spectroscopy%20Hsu (Accessed on 22 October 2024)
5. Kaliva, M., Vamvakaki, M. (2020). Nanomaterials characterization. Polymer Science and Nanotechnology. DOI: 10.1016/B978-0-12-816806-6.00017-0, https://www.sciencedirect.com/science/article/abs/pii/B9780128168066000170
6. Broad Institute. (n.d.). What is Mass Spectrometry? [Online] Broad Institute. Available at https://www.broadinstitute.org/technology-areas/what-mass-spectrometry (Accessed on 22 October 2024)
7. Li, Q., Kang, C. (2020). A Practical Perspective on the Roles of Solution NMR Spectroscopy in Drug Discovery. Molecules. DOI: 10.3390/molecules25132974, https://www.mdpi.com/1420-3049/25/13/2974
8. Hughes, C., Clemens, G., Baker MJ. (n.d.). Preclinical Screening of Anticancer Drugs using Infrared (IR) Micro-spectroscopy. [Online] Available at https://pure.strath.ac.uk/ws/portalfiles/portal/43497336/Hughes_etal_TIB_2015_Preclinical_screening_of_anticancer_drugs_using_infrared.pdf (Accessed on 22 October 2024)
9. Yang, S., Kar, S. (2023). Application of artificial intelligence and machine learning in early detection of adverse drug reactions (ADRs) and drug-induced toxicity. Artificial Intelligence Chemistry. 10.1016/j.aichem.2023.100011, https://www.sciencedirect.com/science/article/pii/S2949747723000118
10.  Tavana, B., Chen, A. (2022). Determination of Drugs in Clinical Trials: Current Status and Outlook. Sensors. DOI: 10.3390/s22041592, https://www.mdpi.com/1424-8220/22/4/1592
11. Raj, N., et al. (2019). Postmarket surveillance: a review on key aspects and measures on the effective functioning in the context of the United Kingdom and Canada. Therapeutic Advances in Drug Safety. DOI: 10.1177/2042098619865413, https://journals.sagepub.com/doi/full/10.1177/2042098619865413
12.  Gyamfi, D., et al. (2024). In-Process Quality Checks and Post-Market Surveillance of Artemether-Lumefantrine Fixed-dose Combination Tablets and Suspensions: Current Procedures, Successes, Advances, and Challenges. Journal of Advances in Medical and Pharmaceutical Sciences. DOI: 10.9734/jamps/2024/v26i7698, http://archive.jibiology.com/id/eprint/2485/

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