A new doctoral thesis at Karlstad University provides increased understanding of how medicines can be analysed more reliably and safely. The research focuses on fundamental investigations of liquid chromatography, one of the most important analytical techniques used in the pharmaceutical industry. This type of fundamental understanding is essential, as many current challenges cannot be solved by empirical method optimisation alone.
Liquid chromatography is used to separate and measure the different components of a medicine. In addition to the active substance, medicines often contain excipients that stabilise the product and determine its final form. To establish the correct dosage and detect harmful substances, the active ingredient must first be separated from these other components.
“Charged molecules are generally more difficult to analyse than uncharged molecules in liquid chromatography. While many traditional drugs carry a single charge, newer therapeutics such as oligonucleotides and peptides often carry multiple charges, making their analysis significantly more challenging,” says Abdul Haseeb, Doctor of Analytical Chemistry and author of the thesis Fundamental Investigations of Retention and Adsorption in LC with Emphasis on Charged Solutes.
Challenging molecules
When medicines are analysed using liquid chromatography, some drug molecules can be difficult to work with. This is especially true for molecules that carry an electrical charge. They tend to interact in complex ways with the stationary phase inside the chromatographic column, which often leads to poor peak shape and less reliable results.
In practice, this can mean that unwanted substances, such as degradation products or impurities, are not properly separated from the active drug ingredient. This can, in turn, affect both the safety and efficacy of the medicine.
One unexpected finding of the research is that certain active sites in the column (residual silanols)—previously seen mainly as a problem—can actually be beneficial if they are carefully controlled and used in the right way.
“Instead of trying to eliminate these active sites completely, they can be used to improve peak shape, enhance separation, and produce more reliable analytical results,” says Abdul Haseeb.
Important for future medicines
The research is particularly relevant for new types of medicines, such as oligonucleotides and peptides, which are used to treat genetic and previously hard‑to‑treat diseases. These are large molecules with multiple charges and place very high demands on purity and analytical characterization.
“Our work shows that a deeper mechanistic understanding of chromatographic processes is necessary to develop robust analytical methods for modern medicines. This is crucial for ensuring that new types of medicines can be accurately analysed, used safely by patients, and approved by regulatory authorities,” says Abdul Haseeb.
