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ABSTRACTA new selective and sensitive high‐performance liquid chromatography (HPLC) method was developed for the quantification of potential impurities in fluoxetine hydrochloride. Chromatographic separation was achieved on an end‐capped octadecylsilyl silica gel (Gemini‐C18 150 mm × 4.6 mm, 3.0 μm) using a gradient program with triethylamine, methanol, and water as the mobile phase at a flow rate of 1.0 mL/min and monitored at 215 nm. The run time was 60 min. The method was validated to fulfill International Conference on Harmonization (ICH Q2(R2)) requirements, and this validation included specificity, precision, linearity, limit of detection (LOD), limit of quantification (LOQ), and accuracy. The calibration curve was linear over the concentration range from LOQ to 120% with respect to sample concentration. The accuracy of the method is within the acceptable limit of 80%–120%. The results obtained for all parameters were within the acceptance criteria. So, this method can be employed for the regular analysis of potential impurities in the fluoxetine hydrochloride API.

ABSTRACTEnantioseparation and enantiorecognition are crucial in the pharmaceutical analysis of chiral substances, impacting safety, efficacy, and regulatory compliance. Enantioseparation refers to the process of separating enantiomers from a mixture, typically achieved through chromatography techniques like HPLC and SFC. In contrast, enantiorecognition involves the identification of enantiomers based on their interaction with a chiral selector without the need for separation. Recent advancements in these techniques have significantly improved enantioseparation efficiency and resolution. Chiral stationary phases (CSPs) have evolved, offering better selectivity, including hybrid organic–inorganic materials and miniaturization. The use of green solvents has also reduced environmental impact. Non‐chromatographic methods, such as circular dichroism (CD) and nuclear magnetic resonance (NMR) spectroscopy, enable enantiorecognition through interactions with polarized light or chiral solvents. However, these methods face challenges, including high costs, limited solvent compatibility, and shorter operational lifespans compared with chromatographic techniques. Recent developments in solvent‐tolerant hybrid CSPs aim to address these limitations. This review highlights these innovations, focusing on their relevance to the pharmaceutical industry, pollution control, and quality assurance, and emphasizes the growing importance of these techniques in the production and regulation of chiral drugs.

Abstract Cinnarizine (CIN) drug substance is a US FDA and EMA approved antihistaminic drug, There is no report available on CIN for the identification of degradation products and their degradation pathway. Herein, we report a stability‐indicating assay method for CIN, the formation and characterization of its major degradation products using LC‐HRMS/MS and 1H‐NMR techniques. CIN was subjected to oxidation, acid, base, thermal and photolytic degradation conditions. Two unknown degradation products (DP‐1 and DP‐2) of CIN were formed under oxidative conditions. We successfully separated these degradants using gradient elution on an Inertsil ODS 3 V column (150 × 4.6 mm, 5 μm) using mobile phase A consisting of 0.1% formic acid and the mobile phase B consisting of 0.1% formic acid/acetonitrile (20/80, v/v). CIN was labile to oxidative conditions and stable to acidic, alkaline hydrolytic, photolytic and thermal conditions. The degradation pathways were derived from the nature of the product formed under oxidative degradation conditions and available reports for confirmation of the mechanism. Since the stability‐indicating assay method can be utilized for stability studies and routine quality control of CIN in both the pharmaceutical industry and research laboratories. This method has been validated in compliance with the guidelines set forth by the ICH.

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Hong-Hua-Xiao-Yao tablet (HHXYT) is attracting attention increasingly because of its use in treatment of mammary gland hyperplasia (MGH) and menopausal syndrome. However, its pharmacokinetics remains unclear. This study developed a sensitive and rapid method for simultaneous determination of 10 compounds of HHXYT in rat plasma by liquid chromatography-tandem mass spectrometry and to compare the pharmacokinetics of these compounds in MGH rats and sham operated rats. The linearity, accuracy, precision, stability and matrix effect were within acceptable ranges. This established method was successfully applied to a pharmacokinetics study of 10 compounds in sham operated and MGH rats. According to the results, the bioavailability of glycyrrhetinic acid was highest in MGH rats and sham operated rats. The mean residence times of glycyrrhetinic acid and glycyrrhetinic acid 3-O-glucuronide were higher than those of the other compounds while the mean residence time and half-life of liquiritin, isoliquiritin and paeoniflorin were lower. Some pharmacokinetic parameters of ormononetin, liquiritigenin, isoliquiritigenin, liquiritin, isoliquiritin, paeoniflorin, protocatechuic acid and senkyunolide I were significantly different between MGH rats and sham operated rats. This study elucidated the dynamic changes of multiple components in rats after oral administration of HHXYT systematically and comprehensively, which provided guidance for clinical application.

N-acetyl-l-cysteine (NAC) shows beneficial effects in cases of aflatoxicosis and heat stress in poultry but little is known about its pharmacokinetics in chickens. Therefore, the study aimed to develop and validate a sensitive LC-MS/MS analytical method for quantitative analysis of NAC in chicken plasma. A split calibration curve approach was used for determination of NAC in chicken plasma. Standard curves for low (0.05-2.5μg/ml) and high (2.5-100 μg/ml) ranges of concentrations were prepared. The standard curves for low (r2 = 0.9987) and high (r2 = 0.9899) concentrations were linear within the tested range. The limits of detection (LOD) and of quantification (LOQ) for the standard at low concentrations were 0.093 and 0.28 μg/ml, respectively. The accuracy was from 97.35 to 101.33%. The values of LOD and LOQ for the standard at high concentrations were 0.76 and 2.30 μg/ml, respectively. The accuracy was between 99.77 and 112.14%. The intra- and inter-day precisions for all concentrations from both standards did not exceed 8.57% and 10.69%, respectively. The recovery for all concentrations was between 92.45 and 105.52%. The validated method for determination of NAC in chicken plasma can be applied in future pharmacokinetic studies in chickens without dilution of samples and their repeated analysis.

Nirmatrelvir (NRV), a 3C-like protease or Mpro inhibitor of SARS-CoV-2, is used for the treatment of COVID-19 in adult and paediatric patients. The present study was accomplished to investigate the comprehensive metabolic fate of NRV using in vitro and in vivo models. The in vitro models used for the study were microsomes (human liver microsomes, rat liver microsomes, mouse liver microsomes) and S9 fractions (human liver S9 fractions and rat liver S9 fractions) with the appropriate cofactors, whereas Sprague-Dawley rats were used as the in vivo models. Nirmatrelvir was administered orally to Sprague-Dawley rats, which was followed by the collection of urine, faeces and blood at pre-determined time intervals. Protein precipitation was used as the sample preparation method for all the samples. The samples were then analysed by liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (LC-Q-ToF-MS/MS) using an Acquity BEH C18 column with 0.1% formic acid and acetonitrile as the mobile phase. Four metabolites were found to be novel, which were formed via amide hydrolysis, oxidation and hydroxylation. Furthermore, an in silico analysis was performed using Meteor Nexus software to predict the probable metabolic changes of NRV. The toxicity and mutagenicity of NRV and its metabolites were also determined using DEREK Nexus and SARAH Nexus.

In recent years, researchers have shown a growing interest in the interactions between different pharmaceutical agents. An intriguing instance lies in the possible interaction between nimodipine and vitamin C. To investigate the pharmacokinetic and pharmacodynamic effects of vitamin C on nimodipine in rats, rats were randomly divided into a nimodipine only group and a combination group (nimodipine + vitamin C). The two groups were given intragastric administration and nimodipine blood concentrations were determined using high-performance liquid chromatography-tandem mass spectrum at different time points. Blood pressure and heart rate were measured via carotid artery cannulation. Pharmacokinetic differences were observed between the nimodipine only group and the combination group at the same dose. Compared with the nimodipine only group, the combination group's main pharmacokinetic parameters of peak concentration and area under the curve increased significantly, and the difference was statistically significant (p < 0.05); furthermore, the combination group exhibited a significant reduction in average blood pressure, while no significant effects on heart rate were observed. Vitamin C did not affect the activity of CYP450 in rat liver. The pharmacokinetic characteristics and pharmacodynamics of nimodipine were changed by vitamin C administration in rats.

No abstract is available for this article.