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Exploring the Use of Humanized Mouse Models in Drug Safety Evaluation

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  The purpose of drug development is to find new safe, effective drugs of high quality and stability to cure diseases and save lives. Developing a new drug is a very complex process, but it can be divided into  preclinical research   and clinical studies of a new drug.  Preclinical research is the first challenge in  drug development , and preclinical toxicity studies of new medicines are an essential part of the journey from the laboratory to the clinic. Since many studies closely related to the safety of subjects, such as drug distribution, reproductive toxicity, and carcinogenicity studies, cannot be performed on issues in clinical trials, animal experiments have an irreplaceable role.  However, there are differences between animals and humans, safety studies cannot be conducted on animal models alone, and normal animals do not respond to drugs the same way as patients. The humanized mouse model solves this challenge to some extent. Preclinical stu...

Pharmacological effects and metabolite analysis of Matrine

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 The metabolite content of drugs in organisms is minimal, and it is not easy to isolate and prepare pure products. The metabolite structure is complex, and it is also challenging to obtain metabolites by chemical synthesis. Thus the study of metabolite analysis of drugs in organisms is minimal. Bitter ginseng is the dried root of bitter legume ginseng. The secondary metabolites currently isolated from bitter ginseng are mainly alkaloids and flavonoids, in addition to a few phenolic, triterpenoid, phenylpropanoid, fatty acid, and amino acid components. Domestic and foreign research focuses on its alkaloid components. The alkaloids extracted, isolated, and identified from the bitter ginseng plant now include bitter ginseng alkaloids, oxymatrine, iso-bitter ginseng alkaloids, hydroxy bitter ginseng alkaloids, lacustrine, oxymatrine, etc.  Metabolite identification refers to identifying and characterizing the small molecules (metabolites) present in a biological sample, such as b...

The role of mass spectrometry in drug metabolite analysis

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 Mass spectrometry is an essential technique for performing drug metabolite analysis , which is characterized by high detection sensitivity, a wide range of molecular masses analyzed, and a large amount of molecular structure information provided. Moreover, mass spectrometry is often used in conjunction with other analytical methods, such as chromatography and electrophoresis, which further expands the application of mass spectrometry. For example, some researchers have used ultra-high pressure liquid chromatography-time-of-flight mass spectrometry for metabolite analysis of drugs in rats to investigate the substances that exert drug effects. 1. Mass spectrometry can be used for drug metabolite analysis Drug metabolites are derived from the metabolic reactions of drugs, and the structure of metabolites is closely related to the type of metabolic reactions and the structural properties of precursor compounds. After the metabolic transformation of a drug in vivo, only some structural...

Drug metabolism studies can explore drug toxicity and toxic mechanism of action.

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 In drug development, many compounds often die in clinical trials because of the toxicity or safety of their metabolites, among which the active metabolites formed by drug molecules activated by human liver metabolism are more likely to be an important cause of toxicity.  In vivo or in vitro metabolite analysis of drugs can be used to determine an early stage whether a compound is toxic and suitable for further development, thus minimizing unnecessary losses. In preclinical drug metabolite analysis and metabolite structure identification to evaluate the safety of a drug metabolite, one can identify an animal species in a routine toxicology test in which adequate exposure levels of that metabolite can be formed, which is comparable to or higher than human exposure, and then study the drug toxicity in that animal species. Alternatively, if a relevant animal species cannot be identified that forms the metabolite, the metabolite can be synthesized, and further safety evaluations ...