Unlocking the Potential of Pharmaceutical Impurities
A new methodology and protocol to increase the scope of essential pharmaceutical analysis during the production and testing of drug molecules.
cassis/stock.adobe.com
During the production and testing of drug molecules, numerous impurities are removed to protect users from potentially toxic compounds, however, some impurities prove not to be toxic and could in fact have their own therapeutic potential. As such, researchers have developed a new methodology and protocol to increase the scope of essential pharmaceutical analysis to include drug discovery (1).
The drug discovery landscape is an increasingly demanding but fundamental part of the pharmaceutical industry, which constantly seeks new technologies to speed up all steps of the drug discovery process. Structure-based computational assessments are increasingly being relied on for the prediction of toxicity and biological activities, and bridging the gap between drug discovery and pharmaceutical analysis requires methods for the characterization of compounds produced during pharmaceutical drug production. As such, researchers developed a protocol and examined its potential by characterizing the major degradation products of zileuton (ZLT), which is a 5-lipooxygenase (5-LOX) inhibitor used for the treatment of asthma.
The initial degradation products were resolved using an ultra-high-pressure liquid chromatography photo-diode-array (UHPLC‑PDA) protocol, which was validated in a previous study (2). ZLT, along with acid- and alkali-stressed samples, were then subjected to liquid chromatography–mass spectrometry quadrupole time-of-flight (LC–MS-QTOF) studies. Major degradation products were isolated using preparative thin layer chromatography (PTLC) and characterized using QTOF and/or Proton nuclear magnetic resonance (1H NMR) studies. The information obtained was assembled for structural conformation.
Toxicology prediction software identified some compounds as non-toxic and hence they could be explored as therapeutic targets as they may have potential bio-therapeutic uses. Further analysis using three-dimensional extra precision (3D-XP)-molecular docking explored the changes in the bio-affinity of the degradation productions for the 5-LOX enzyme, with one product being found to have a higher binding affinity than the drug itself indicating it could potentially be a suitable anti-asthmatic.
Further to this, the products were evaluated for activity at other sites using prediction of activity spectra for substances (PASS) with some products being predicted antineoplastic, antiallergic, and inhibitors of complement factor-D, making them a potential antitumour agent.
References
- S.B. Ganorkar et al., J. Pharm. Biomed. Anal. 179, 112982 (2020).
- S.B. Ganorkar, D.M. Dhumal, and A.A. Shirkhedkar, Arab. J. Chem. 10, 273–282 (2017).
The Next Frontier for Mass Spectrometry: Maximizing Ion Utilization
January 20th 2025In this podcast, Daniel DeBord, CTO of MOBILion Systems, describes a new high resolution mass spectrometry approach that promises to increase speed and sensitivity in omics applications. MOBILion recently introduced the PAMAF mode of operation, which stands for parallel accumulation with mobility aligned fragmentation. It substantially increases the fraction of ions used for mass spectrometry analysis by replacing the functionality of the quadrupole with high resolution ion mobility. Listen to learn more about this exciting new development.
Liquid Chromatography to Analyze Vitamin D Proteins in Psoriasis Patients
January 21st 2025Can a protein involved in delivering Vitamin D to target tissues have an altered serum profile in psoriasis patients with cardiovascular disease? Researchers used liquid chromatography (LC) to help find out.
The Complexity of Oligonucleotide Separations
January 9th 2025Peter Pellegrinelli, Applications Specialist at Advanced Materials Technology (AMT) explains the complexity of oligonucleotide separations due to the unique chemical properties of these molecules. Issues such as varying length, sequence complexity, and hydrophilic-hydrophobic characteristics make efficient separations difficult. Separation scientists are addressing these challenges by modifying mobile phase compositions, using varying ion-pairing reagents, and exploring alternative separation modes like HILIC and ion-exchange chromatography. Due to these complexities, AMT has introduced the HALO® OLIGO column, which offers high-resolution, fast separations through its innovative Fused-Core® technology and high pH stability. Alongside explaining the new column, Peter looks to the future of these separations and what is next to come.
A Guide To Finding the Ideal Syringe and Needle
January 20th 2025Hamilton has produced a series of reference guides to assist science professionals in finding the best-suited products and configurations for their applications. The Syringe and Needle Reference Guide provides detailed information on Hamilton Company’s full portfolio of syringes and needles. Everything from cleaning and preventative maintenance to individual part numbers are available for review. It also includes selection charts to help you choose between syringe terminations like cemented needles and luer tips.
