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Liquid chromatography coupled to mass spectrometry already started to surpass the major drawbacks in terms of sensitivity, specificity and cross-reactivity that some analytical methods used in the clinical laboratory exhibit. This hyphenated technique is already preferred for specific applications while finding its own place in the clinical laboratory setting. However, large-scale usage, high-throughput analysis and lack of automation emerge as shortcomings that liquid chromatography coupled to mass spectrometry still has to overrun in order to be used on a larger scale in the clinical laboratory. The aim of this review article is to point out the present-day position of the liquid chromatography coupled to mass spectrometry technique while trying to understand how this analytical method relates to the basic working framework of the clinical laboratory. This paper offers insights about the main regulation and traceability criteria that this coupling method has to align and comply to, automation and standardization issues and finally the critical steps in sample preparation workflows all related to the high-throughput analysis framework. Further steps are to be made toward automation, speed and easy-to-use concept; however, the current technological and quality premises are favorable for chromatographic coupled to mass spectral methods. [ABSTRACT FROM AUTHOR]

Vildagliptin (VIL) is a dipeptidyl peptidase-4 inhibitor used in the treatment of type 2 diabetes mellitus; in therapy, it is available as the enantiomerically pure S-VIL, the other enantiomer R-VIL being considered as an enantiomeric impurity. A systematic screening of 16 cyclodextrin (CD) derivatives as chiral selectors was performed at three pH levels using phosphate (pH 2.5, pH 7.0) and acetate (pH 4.5) buffers. Method optimization employed an experimental design approach, systematically investigating the effect of buffer and CD concentration, buffer pH, capillary temperature, and applied voltage on the chiral resolution and analysis time. The method's analytical performance was thoroughly assessed and subsequently employed for determining the enantiomeric purity of VIL in a pharmaceutical formulation. The properties of the inclusion complexes, such as stoichiometry and atomic level intermolecular host–guest interactions were studied by NMR measurements and molecular modeling. Native α-CD at acidic pH has demonstrated its exceptional suitability for the separation of VIL enantiomers with a favorable migration order (R-VIL followed by S-VIL). The optimized analytical conditions (75 mM acetate buffer, pH 4.5, containing 50 mM α-CD, 18 kV applied voltage, and 15 °C capillary temperature) provided a baseline separation of VIL enantiomers within 9 min. The developed method represents a cost-effective alternative to the enantiomeric impurity control of VIL. Symmetry is often a fundamental aspect of molecular structures and interactions, and our detailed analysis of the chiral recognition process contributes to the understanding of symmetry-related aspects in molecular systems. This developed method not only offers a cost-effective alternative for the enantiomeric impurity control of VIL but also provides valuable information regarding the mechanism of the chiral recognition process, aligning with the broader themes of symmetry in molecular sciences. [ABSTRACT FROM AUTHOR]

Photochemical degradation of drugs can lead to degradation products with potential toxic or allergizing effects for the human body. A significant amount of work has been carried out over the past few decades to clarify the molecular mechanism of photosensitizing processes observed after the administration of certain drugs and exposure to light. There is a close relation between the photosensitizer effect of a drug and its chemical structure. Compounds possessing certain moieties and functional groups in their molecular structure, like aromatic chromophore systems or photo-dissociable bonds that can form free radicals, and consequently are susceptible to have light-induced adverse effects. Photoionization, photodissociation, photoaddition and photoisomerization are the main chemical processes, which can occur during the photochemical decomposition of a pharmaceutical compound. The current study is a short review describing photochemical degradation of certain pharmaceuticals, presenting specific examples from various pharmaceutical classes for the different types of decomposition mechanisms. In vivo methods and clinical tests available for the investigation of photosensitizing reactions are also discussed. [ABSTRACT FROM AUTHOR]

A direct HPLC method was developed for the enantioseparation of pantoprazole using macrocyclic glycopeptide‐based chiral stationary phases, along with various methods to determine the elution order without isolation of the individual enantiomers. In the preliminary screening, four macrocyclic glycopeptide‐based chiral stationary phases containing vancomycin (Chirobiotic V), ristocetin A (Chirobiotic R), teicoplanin (Chirobiotic T), and teicoplanin‐aglycone (Chirobiotic TAG) were screened in polar organic and reversed‐phase mode. Best results were achieved by using Chirobiotic TAG column and a methanol‐water mixture as mobile phase. Further method optimization was performed using a face‐centered central composite design to achieve the highest chiral resolution. Optimized parameters, offering baseline separation (resolution = 1.91 ± 0.03) were as follows: Chirobiotic TAG stationary phase, thermostated at 10°C, mobile phase consisting of methanol/20mM ammonium acetate 60:40 v/v, and 0.6 mL/min flow rate. Enantiomer elution order was determined using HPLC hyphenated with circular dichroism (CD) spectroscopy detection. The online CD signals of the separated pantoprazole enantiomers at selected wavelengths were compared with the structurally analogous esomeprazole enantiomer. For further verification, the inline rapid, multiscan CD signals were compared with the quantum chemically calculated CD spectra. Furthermore, docking calculations were used to investigate the enantiorecognition at molecular level. The molecular docking shows that the R‐enantiomer binds stronger to the chiral selector than its antipode, which is in accordance with the determined elution order on the column—S‐ followed by the R‐isomer. Thus, combined methods, HPLC‐CD and theoretical calculations, are highly efficient in predicting the elution order of enantiomers. [ABSTRACT FROM AUTHOR]

Photochemical degradation of drugs can lead to degradation products with potential toxic or allergizing effects for the human body. A significant amount of work has been carried out over the past few decades to clarify the molecular mechanism of photosensitizing processes observed after the administration of certain drugs and exposure to light. There is a close relation between the photosensitizer effect of a drug and its chemical structure. Compounds possessing certain moieties and functional groups in their molecular structure, like aromatic chromophore systems or photo-dissociable bonds that can form free radicals, and consequently are susceptible to have light-induced adverse effects. Photoionization, photodissociation, photoaddition and photoisomerization are the main chemical processes, which can occur during the photochemical decomposition of a pharmaceutical compound. The current study is a short review describing photochemical degradation of certain pharmaceuticals, presenting specific examples from various pharmaceutical classes for the different types of decomposition mechanisms. In vivo methods and clinical tests available for the investigation of photosensitizing reactions are also discussed., (©2022 The Authors.)