Current Issue : April-June Volume : 2026 Issue Number : 2 Articles : 5 Articles
Protein-based APIs represent a big group of modern therapeutics. Their characterization involves complex analytical protocols which require special methods, especially in the case when the protein drug is included into tablet dosage forms. Although the fluorescence polarization assay (FPA) is not currently regulated by many national Pharmacopeias, it represents a promising approach for protein drug standardization, considering their rapid, sensitive, and automatable detection suitable for high-throughput analysis and real-time quality control. To evaluate the applicability of FPA for the analysis of protein drugs in tablets, the quantifying of lysozyme in tablet dosage forms was studied by this method with the use of a fluorescently labeled synthetic chitooligosaccharide tracer. It was shown that this approach overcomes the limitations of the conventional turbidimetric assay of lysozyme determination, which is labor-intensive and relies on unstable reagents. Measurements were performed with both portable and stationary fluorescence polarization readers. Commercial tablets from five manufacturers containing lysozyme (20 mg) and pyridoxine hydrochloride (10 mg) together with other excipients were analyzed. The FPIA method showed a linear range of 5.0–70 μg/mL, with specificity confirmed by the absence of interference from excipients. Accuracy, evaluated by standard addition (10–20 mg), yielded recoveries of 100.2–106.0%. Placebo spiked with lysozyme at 80–120% of nominal content demonstrated recoveries of 98.0–100.1%, with RSD (n = 6) not exceeding 13.7%, indicating good precision. The developed method enables reliable lysozyme quantification in tablets, offering speed, simplicity, and robustness, and shows its suitability for the routine quality control of protein-containing dosage forms including the enzyme ones....
Desloratadine (DL) and montelukast sodium (MTS) are combined in a pharmaceutical preparation for the treatment of allergic rhinitis and asthma. DL is a competitive H1-receptor antagonist and helps the management of allergic reactions and relieves allergy symptoms, while MTS is a leukotriene receptor antagonist that inhibits the effects of inflammatory mediators. This study introduces a machine learning-assisted UV-Vis spectrophotometric method for the simultaneous quantification of DL and MTS in a commercial film-coated tablet, addressing limitations due to spectral overlap. Five machine learning regression models (Support Vector Regression, Ridge Regression, Lasso Regression, Elastic Net, and Linear Regression) were evaluated. Ridge Regression (λ = 0.1) was selected for its balance of accuracy, computational efficiency, and robustness. The method was applied using Aircomb® film-coated tablets, containing 5 mg DL and 10.4 mg MTS, ensuring high precision. The developed method demonstrated high recovery rates (99.25% for DL and 101.0% for MTS with minimal relative standard deviation (≤ 1.59%). Sustainability assessments using Analytical GREEnness Metric (AGREE) and Complex Green Analytical Procedure Index (ComplexGAPI) confirmed its alignment with green analytical chemistry principles. Ridge Regression (λ = 0.1) provided accurate and reproducible results, making it suitable for routine pharmaceutical analysis. This study highlights the potential of machine learning-assisted UV-Vis spectrophotometry as a cost-effective and environmentally friendly alternative for pharmaceutical quality control. The method minimizes solvent consumption while ensuring analytical precision. Future research may explore non-linear models, such as artificial neural networks, to enhance predictive performance and broaden its applicability....
As one of the key components in technetium-labeled radiopharmaceuticals, the quality of the dimercaptosuccinate (DMSA) plays a critical role in determining the safety and efficacy of the final drug product. However, due to its high polarity and susceptibility to oxidation, comprehensive characterization of the impurity profile of DMSA remains challenging. In this study, high-performance liquid chromatography and mass spectrometry were employed to achieve a systematic and thorough analysis of DMSA-related impurities. First, an HPLC-UV method was developed to enable baseline separation of DMSA and its impurities. Subsequently, a two-dimensional liquid chromatography–tandem mass spectrometry (2D-LC-MS/MS) approach was applied to identify six structurally diverse impurities present in DMSA. The developed HPLC method was rigorously validated and demonstrated to be sensitive, robust, and suitable for the accurate quantification and detection of trace impurities. Using the validated method, DMSA raw materials sourced from multiple manufacturers were analyzed, revealing significant variability in their impurity profiles. These findings underscore the importance of stringent quality control measures for DMSA in radiopharmaceutical manufacturing. This work not only establishes a reliable analytical framework for impurity profiling and structural elucidation of DMSA but also provides valuable insights for the development of quality control strategies and process optimization of radiopharmaceuticals....
Background/Objectives: Nitrosamine drug substance-related impurities (NDSRIs) are a class of potent genotoxic impurities that pose a critical risk to patient safety, thereby necessitating the stringent control of pharmaceutical products. Nortriptyline (NORT) and sertraline (SERT) are two widely prescribed antidepressants that form highly potent NDSRIs, N-nitroso-nortriptyline (NNORT) and N-nitroso-sertraline (NSERT), respectively. Despite these risks, a substantial gap exists in terms of the validated analytical methods for surveillance. Accordingly, this study addressed this need by developing a liquid chromatography–tandem mass spectrometry method for the quantification of NNORT and NSERT in drug products. Methods: A comparative evaluation of two reversedphase columns (general-purpose C18 column and phenyl-hexyl column) was performed to achieve optimal chromatographic resolution of the parent active pharmaceutical ingredients (APIs). Results: The phenyl-hexyl column demonstrated superior separation for both NDSRI/API pairs by leveraging π-π interactions to markedly enhance the resolution. This was particularly critical for SERT. The method was fully validated according to the International Council for Harmonization guideline Q2(R1) and demonstrated excellent linearity (r2 = 0.998 for both NNORT and NSERT) with limits of quantitation of 20 ng/g for NNORT and 125 ng/g for NSERT. Accuracy was confirmed with recoveries of 96.6–99.4% for NNORT and 98.6–99.4% for NSERT, and precision was acceptable, with relative standard deviation below 3.9% and 1.9%, respectively. The application of this method to commercial products subjected to accelerated stress testing revealed NNORT formation in NORT products with an average concentration of 190 ng/g, as well as NSERT formation in SERT products resulted in an average concentration of 172 ng/g. Conclusions: This validated method provides a reliable tool for routine quality control, thereby enabling pharmaceutical manufacturers and regulatory agencies to ensure safety and compliance with widely used antidepressant medications....
A robust and stability-indicating Reverse Phase-High Performance Liquid Chromatography (RP-HPLC) method was developed and validated for the quantitative determination of bexagliflozin and its related impurities in accordance with the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH Q2(R1)) guidelines. Chromatographic separation was achieved on a C18 column using a mobile phase of methanol and ammonium acetate buffer (pH 4.2) in a 60:40 (v/v) ratio, with a flow rate of 1.0 mL·min−1 and UV detection at 220 nm. The method was validated for linearity, sensitivity (LOD and LOQ), precision, robustness, and system suitability, all within acceptable limits for low-concentration analysis. Excellent linearity (r2 > 0.999) and precision (%RSD 0.3–4.4%) confirmed its reliability for stability assessment. The assay was performed at 100 μg·mL−1, where all validation parameters showed %RSD values ≤ 2%, demonstrating high precision and robustness. Forced degradation studies under acidic, basic, oxidative, photolytic, and thermal conditions revealed a major degradation product formed under acidic stress. This product was isolated and structurally characterized using LC–MS, 1H NMR, and 13C NMR, and is reported here for the first time. The proposed RP-HPLC method proved to be specific, precise, and reliable for the determination of bexagliflozin and its related impurities, making it suitable for routine stability testing, quality control, and pharmaceutical development applications....
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