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Kisspeptin-10 is a peptide hormone capable of increasing circulating follicle-stimulating hormone, luteinizing hormone and testosterone levels in humans. Clinically, these effects suggest its use as a treatment for infertility. However, its testosterone-increasing effect indicates potential misuse in sports. As such, it is included in the 2024 World Anti-Doping Agency Prohibited List. This work describes the successful validation of an initial testing procedure (screening) and a confirmation procedure for kisspeptin-10 in urine using liquid chromatography-mass spectrometry. Additionally, kisspeptin-10 was incubated in human serum to mimic endogenous metabolism to improve method sensitivity, as previous research had demonstrated a rapid elimination time of only 30 min after injection (in rats). Four metabolites, corresponding to peptide fragments y9, y8, y7 and y5, were found and added to the ITP in full scan mode. A degradation product discovered during early experimentation was found to probably be caused by oxidation of the tryptophan residue into a kynurenine residue. Further research should elucidate the kinetic parameters of the reaction to improve product stability. Using the validated confirmation procedure, a black-market vial of kisspeptin-10 was analysed. The product contained no unexpected impurities, although it appeared to have undergone more degradation than the purchased reference standard., (© 2024 John Wiley & Sons Ltd.)

During the last decade, the focus of bioanalytics shifted from the mere analysis of biomacromolecules to the application of proteins and nucleic acids for analytical purposes, e.g. accessing the biological role of cellular constituents, target identification and validation, quantification of receptor-ligand interactions and others. The increasing impact of combining biomacromolecules with standard analytic devices can be exemplified by the central role of DNA and protein micro-arrays in the fields of genomics, proteomics, transcriptomics or pharmacogenomics. Medicinal chemistry is considered as the scientific discipline concerned with the discovery, design, identification, and preparation of biologically active compounds and the interpretation of their mode of action at the molecular level and their metabolites. From this definition it is evident that bioanalytical tools put into service of medicinal chemistry needs can contribute substantially to progress in drug discovery, design and identification, especially in cases when these tools are well-adapted for miniaturisation and automation to enable high throughput screening. Many successful examples of combining biomacromolecules with standard instrumental analytics indicate that the former role of biochemical testing in medicinal chemistry is more and more replaced by what we call molecular bioanalytics. In recent research, we showed how molecular biology methods and whole cell approaches can be integrated into new bioanalytical tools of complex assembly and how these tools are applicable for drug discovery, drug synthesis and high throughput screening. This is exemplified by the evolutive development of enzyme inhibitors for targets in chronic inflammatory diseases (cathepsin G) or cancer (CK2, hyaluronidase).

Antibiotic associated diarrhea (AAD) is a common adverse reaction to most types of antibiotics with frequencies ranging from 5-39%, depending upon the specific type of antibiotic and the presence of other risk factors. The pathogenesis of antibiotic associated diarrhea is mediated through the disruption of the normal flora and overgrowth of pathogens or through metabolic imbalances. Beside risk factors associated with the type and duration of antibiotic therapy, host factors include the extremes of age (< 6 years or > 65 years), severe underlying disease, presence of other chronic intestinal conditions, immunosuppression, prior history of AAD and exposures during recent hospitalizations (surgery, nasogastric tube feeding). Factors which have not been significantly associated with antibiotic associated diarrhea include gender, dose or route of the inciting antibiotic and inflammatory bowel disease. The clinical impact of AAD is reflected by potential severity of the illness (PMC), possible consequences of the disruption in the treatment of the primary infection, higher medical costs, increased hospital stays and increased rates of morbidity and mortality. The key to decreasing these consequences is prompt diagnosis followed by effective treatment and institution of control measures and preventive treatments in patients at risk.