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Advances in techniques for quality analysis allow for a more detailed examination of drug impurities. High‐resolution mass spectrometry (HRMS) contributes to detecting both known and unknown impurities. In this study, a combination of a nontargeted and targeted screening approach was established and applied to the detailed degradation profile of the losartan potassium (LP) drug substance. Through general unknown comparative screening (GUCS), 35 degradation products (DPs) were detected; of these, 10 DPs were confirmed with reference substances. DP‐1, DP‐2, DP‐3, and DP‐6 were the first characterized, as per previous studies; the other twenty‐four were newly identified. In addition, a liquid chromatography‐tandem mass spectrometry method was developed for the determination of the ten DPs. It was sensitive, with the limit of quantitation of analytes ranging from 0.01 to 0.5 ng mL−1. Two newly characterized DPs, DP‐1 and DP‐2, were determined in active pharmaceutical ingredient solutions. This study introduced a new approach using broad screening to analyze degradation impurity profiles in LP drug substance, aiding in the identification of low‐level impurities or those without reference substances. Additionally, the sensitive determination method developed allows for the precise quantification and control of ten DPs at trace levels in LP drug substances or products. [ABSTRACT FROM AUTHOR]

Despite ongoing breakthroughs in novel anticancer therapies, chemotherapy remains a mainstream therapeutic modality in different types of cancer. Unfortunately, chemotherapy-related toxicity (CRT) often leads to dose limitation, and even results in treatment termination. Over the past few years, accumulating evidence has indicated that the gut microbiota is extensively engaged in various toxicities initiated by chemotherapeutic drugs, either directly or indirectly. The gut microbiota can now be targeted to reduce the toxicity of chemotherapy. In the current review, we summarized the clinical relationship between the gut microbiota and CRT, as well as the critical role of the gut microbiota in the occurrence and development of CRT. We then summarized the key mechanisms by which the gut microbiota modulates CRT. Furthermore, currently available strategies to mitigate CRT by targeting the gut microbiota were summarized and discussed. This review offers a novel perspective for the mitigation of diverse chemotherapy-associated toxic reactions in cancer patients and the future development of innovative drugs or functional supplements to alleviate CRT via targeting the gut microbiota. [ABSTRACT FROM AUTHOR]

Introduction Perfluorooctane sulfonate (PFOS) is a ubiquitous environmental pollutant, which has accumulated excessively among the higher trophic level of the food chain through biological concentration and magnification. It has a [...], Background: Perfluorooctane sulfonate (PFOS) is a persistent organic pollutant that can cause hepatotoxicity. The underlying toxicological mechanism remains to be investigated. Given the critical role of fecal microbiota in liver function, it is possible that fecal microbiota may contribute to the liver toxicity induced by PFOS. Objectives: We aimed to investigate the role of liver-fecal microbiota axis in modulating PFOS-induced liver injury in mice. Methods: Male and female mice were exposed to PFOS or vehicle for 14 d. In this investigation, 16S rDNA sequencing and metabolomic profiling were performed to identify the perturbed fecal microbiota and altered metabolites with PFOS exposure. In addition, antibiotic treatment, fecal microbiota transplantation, and bacterial administration were conducted to validate the causal role of fecal microbiota in mediating PFOS-induced liver injury and explore the potential underlying mechanisms. Results: Both male and female mice exposed to PFOS exhibited liver inflammation and steatosis, which were accompanied by fecal microbiota dysbiosis and the disturbance of amino acid metabolism in comparison with control groups. The hepatic lesions were fecal microbiota-dependent, as supported by antibiotic treatment and fecal microbiota transplantation. Mice with altered fecal microbiota in antibiotic treatment or fecal microbiota transplantation experiments exhibited altered arginine concentrations in the liver and feces. Notably, we observed sex- specific lower levels of key microbiota, including Lactobacillus, Enterococcus, and Akkermansia. Mice treated with specific bacteria showed lower arginine levels and lower expression of the phosphorylated mTOR and P70S6K, suggesting lower activity of the related pathway and mitigation of the pathological differences observed in PFOS-exposed mice. Conclusions: Our study demonstrated the critical role of the fecal microbiota in PFOS-induced liver injury in mice. We also identified several critical bacteria that could protect against liver injury induced by PFOS in male and female mice. Our present research provided novel insights into the mechanism of PFOS-induced liver injury in mice. https://doi.org/10.1289/EHP10281