Nanotechnology has greatly promoted the research and development of nanodrugs and nanoparticles, providing new therapeutic options for many diseases. However, due to their special physical and chemical properties and its easy accumulation in the liver, nanodrugs and nanoparticles can also bring potential hepatotoxicity risks to the body. This review summarizes the research progress of hepatotoxicity induced by nanodrugs or nanoparticles in recent years from the following three aspects: liver accumulation and cell-nanodrug interaction, toxic mechanisms and influencing factors of toxicity. Also, we discuss the limitations of the previous studies. This paper aims to provide new insights and references for the related researches on hepatotoxicity and preclinical safety evaluation of nanodrugs and nanoparticles.

Objective: To establish a method for controlling polymer impurities in ceftizoxime sodium for injection. Methods: Ceftizoxime sodium was dissolved in phosphate buffer solution (pH 7.0) to prepare degradation solution. High performance size exclusion chromatography (HPSEC) and column switching-LC/MSn (CS-LC/MSn) were applied to separate and deduce the poor retention impurities in the degradation solution. The specificity of developed HPSEC method was evaluated. A RP-HPLC method for polymer analysis was established with a Phenomenex Gemini C₁₈ column, using phosphate buffer solution (pH 7.0)-acetonitrile as mobile phase under a gradient elution program. The specificity of RP-HPLC method was assessed by two-dimensional chromatography (2D-HPLC) and CS-LC/MSn, and LLOD and LLOQ were also tested. Results: ceftizoxime dimer and the dimer's isomer were deduced in the degradation solution as well as 6 small molecular impurities. Polymer impurities were liable to co-elute with small molecular impurities by HPSEC method, which made a poor quantification accuracy and specificity. Ceftizoxime dimer and the dimer's isomer were detected by RP-HPLC with a sufficient specificity. Conclusion: HPSEC method was not suitable for the quality control of polymer impurities in ceftizoxime sodium for injection, while the RP-HPLC method was specific, which can be applied for polymer impurities. Ceftizoxime degradation solution can be used to identify polymer peaks as the systematic suitability testing solution.

Objective: To mine the security alert signals of neratinib based on the FDA Adverse Event Reporting System (FAERS) database to provide a reference for the safety of clinical medication. Methods: The adverse drug event (ADE) signals data of neratinib from the FAERS database from the third quarter of 2017 to the third quarter of 2021 were collected. The data mining was performed using the reporting odds ratio (ROR) and the proportional reporting ratio (PRR) in the proportional imbalance method. Results: A total of 1 362 ADE reports with neratinib as the primary suspected drug were collected, and 96 neratinib ADE signals were mined; 71 signals were obtained after excluding non-adverse drug reaction signals, involving 13 systems. Among them, a total of 48 new signals were not mentioned in the instructions, accumulating 12 systems. Gastrointestinal disorders ADE entries totaled 2 186 cases, generating 25 signals; new signals from investigations accounted for 85.71% of their total system signals. Daily dose was not an independent risk factor for the occurrence of gastrointestinal disorders and investigations ADE. Logistic regression results showed that a course of treatment ≤7 days was an independent risk factor for the occurrence of gastrointestinal disorders, with statistically significant results (P=0.008); compared to a course of treatment ≤7 days, a course of treatment 1 to 3 months was an independent risk factor for the occurrence of investigations ADE (OR=4.288, 95% CI of 1.342 to 13.703;P=0.014). Conclusion: No matter what daily dose is used, adverse reactions need to be paid attention to. The duration of medication is of great significance to the risk of adverse reactions of neratinib, and pharmaceutical care should be strengthened during clinical medication.

Objective: To develop the determination method of the contents of 3′-hydroxy puerarin, puerarin, puerarin apioside, narirutin, naringin, hesperidin, neohesperidin, and praeruptorin A in Shensu Ganmao tablets (SGT) using high performance liquid chromatography with two-reference multi-component method (TRMC). Methods: The analyses were performed on an Agilent ZORBAX SB-C₁₈ column (250 mm×4.6 mm, 5 μm) using the mobile phase of 0.1% phosphoric acid-acetonitrile in gradient elution mode at a flow rate of 1.0 mL·min^-1. The detection wavelength was 283 nm. Results: Taking puerarin as internal reference, the RCF of 3′-hydroxy puerarin and puerarin apioside are 0.853 and 1.354. Taking naringin as internal reference, the relative correlation factors (RCF) of narirutin, hesperidin, neohesperidin, and praeruptorin A are 1.181, 1.027, 1.002, and 2.188. The RCF showed validated on different experimental conditions. The results of 8 components in SGT were in acceptable limits by using TRMC and the external standard method (ESM). Conclusion: The newly established TRMC can determine the characteristic constituents in Puerariae Lobatae Radix, Citri Reticulatae Pericarpium, Aurantii Fructus, and Peucedani Radix in SGT simultaneously, which can be used for quality control of SGT.

Objective: To optimize the parameters in separation and purification processes of Yixintai total saponins, by using failure mode and effects analysis (FMEA) combined with Box-Behnken response surface design. Methods: The total saponins of Yixintai Compound were purified with macroporous resin (MAR), and the key process parameters of the purification process were screened by FMEA. Taking the recovery rate and mass fraction of saponins as evaluation indicators, the Box-Behnken design was used to optimize the MAR purification process of Yixintai total saponins. The optimal parameters were finally obtained in separation and purification processes of Yixintai total saponins. Results: FMEA determined four influencing factors, including the mass concentration of the sample solution, eluent volume fraction, the adsorption flow rate and the volume of the eluent as the key factors for the separation and purification of total saponins. The P values of the models established by Box-Behnken design were all below 0.05, indicating that the models had good predictive abilities. The obtained best parameters was are as follows: the mass concentration of the sample solution is 0.80 mg·mL^-1, the ethanol volume fraction is 90.0%, the adsorption flow rate is 1.7 BV·h^-1, and the eluent volume is 1.6 BV. Conclusion: The separation and purification method obtained by failure mode analysis combined with Box-Behnken optimization was stable and reliable, with high recovery rate and purity of saponins. This method is suitable for purifying Yixintai total saponins.

3CL protease inhibitors has become the focus of the current research on anti-coronavirus drugs. The analysis of the patent information will help the research and innovation of such anti-coronavirus drugs. This paper analyzes the application trends of anti-coronavirus 3CL protease inhibitor-related patents, the distribution of regional status of patents, important applicants, patented technology themes, progress of key drug development and other factors. We also analyze the development of related patent technologies and aim to help domestic pharmaceutical enterprises carry out innovation and complete the strategic layout.

Based on the characteristics of monoclonal antibody, this paper discusses the key points in the pharmacology and toxicology review of monoclonal antibody combined with our review practice and the technical guidelines issued by regulatory agencies. Recommendations are given on the quality of test substance, selection of related animal species, evaluation of immunogenicity and immunotoxicity, and selection of initial dose for the first human clinical trial, so as to provide general principles for designing scientifically acceptable non-clinical research programs for the sponsors and researchers.

In this paper, a database of international registration standard on natural crude drugs (NCDs) and international registered varieties of NCDs was constructed. In this database, taking NCDs as the research object, and the registration status and technical requirements of NCDs were systematically searched in representative countries and regions such as the United States, the European Union, Japan, South Korea, Singapore, Hong Kong, Brazil, Malaysia and South Africa. And the main information sources, system framework design ideas, methods and characteristics of the database are described in detail. The relevant databases are expected be actively constructed to further accelerate the pace of TCM internationalization taking advantages of knowledge integration, in order to provide strong technical support for TCM to go abroad and serve the world.

Pituitrin, oxytocin and vasopressin, as the drugs related to the posterior pituitary, play an irreplaceable role in clinic. Based on the relevant research results of our laboratory and literature survey, this paper analyzes the research status of quality standard of pituitary hormone-related drugs, and further puts forward revision suggestions, in order to provide reference for the improvement of drug quality standard and ensure the safety of clinical medication.

Objective: To study the factors affecting the whiteness of talc and the relationship between them. Methods: The content of metal elements, particle size and particle size distribution, which affect the whiteness of talc, were measured, and the main factors were speculated by principal component analysis (PCA). The linear regression model was established by SPSS. Results: Using PCA analysis, it is speculated that the main factors are the content of impurity metal calcium and particle size D₉₀. The established linear regression model is: Whiteness=96.457+42.770×Calcium% -0.422×D₉₀, with R² of 0.944 and Adjusted R² of 0.934 (P<0.05). The model was successfully constructed. Conclusion: The whiteness of pharmaceutical excipient talc is affected by its impurity metal calcium content and particle size D₉₀. The established whiteness correlation regression model provides a theoretical basis for whiteness as a visual quantity to control the particle size and impurity metal calcium content in talc production process and preparation. This study also provides a new idea for the study of the characteristics and quality attributes of pharmaceutical excipient talc.