To establish a method for determination of polymer impurities in penicillin sodium for injection.

Penicillin sodium was dissolved by water to prepare penicillin polymer stock solution. High performance size exclusion chromatography method (HPSEC) and column switching-LC/MSn method were used to separate and deduce the weak retention impurities in polymer impurity solution and the specificity of HPSEC method was evaluated. A RP-HPLC method for polymer analysis was established with a C₁₈ column, using gradient elution by the mixed solution [phosphate buffer solution (pH 3.4)-methanol (72∶14)] and acetonitrile, and the RP-HPLC method was validated.

4 polymers, their isomers, one dimer degradation and some small molecular impurities were identified in the polymer impurity solution. Polymer impurities were liable to be co-eluted with small molecular impurities by HPSEC method, which resulted in poor quantification accuracy and specificity. 3 indicative polymer impurities were detected by RP-HPLC method with effective specificity, including 2 dimers produced by different polymerized patterns.

HPSEC cannot effectively control the polymer impurities of penicillin sodium for injection. The established RP-HPLC method has good specificity and high sensitivity for the determination of impurities in penicillin sodium polymer for injection.

To improve the quality standards of Mongolian medicine Shashen Zhike Decoction Powder.

TLC method was used to establish the identification of Bistortae Rhizoma and Shikonin, and the identification of Glycyrrhizae Radix et Rhizoma was revised. The content determination of glycyrrhizic acid was established by reversed phase HPLC.

The TLC identification methods resulted in clear spots of Bistortae Rhizoma, Shikonin and Glycyrrhizae Radix Et Rhizoma, without interference for the negative control. Glycyrrhizic acid had good linear relationship in the range from 92.90 to 1 161.25 ng (r=0.999 9). The average recovery was 102.57%, and the RSD was 1.85% (n=9).

The method is simple, specific, stable and repeatable, and can be used for the quality evaluation and control of Shashen Zhike Decoction Powder.

To evaluate and compare the safety and efficacy of microecological live bacteria preparations Lactasin (Lactasin strain) and Biofermin (Biofermin strain) production strains at the genome level using high-throughput sequencing and bioinformatics technology, thus to provide basis for the quality research and consistency evaluation of strains used in the production of ecological live bacteria products.

Combined with a personalized database, DIAMOND retrieval strategy was used to find target genes and analyze their functions through sequence comparison.

The strains used for Lactasin and Biofermin production were both Enterococcus faecium. The genomes of the 2 strains had good collinearity, but a few of genes had rearrangements such as insertions, deletions, inversions, and translocations. The safety of the Biofermin strain was similar to the Lactasin strain in 6 aspects, including virulence genes, drug resistance genes, bacteriocin genes, biogenic amine genes, prophages and mobile genetic elements. In the evaluation of probiotic function of stress response genes, antimicrobial/antagonistic activity, antioxidant activity genes and adhesion genes, Biofermin strain was better than Lactasin strains.

In this paper, a quality evaluation method of strains for the production of microecological live bacteria products was initially established based on specific gene function analysis, and the quality research and quality evaluation system were also improved and perfected for microecological live bacteria products.

To explore the feasibility of multivariate data analysis (MVDA) in formulation robustness study of biopharmaceutical drug products by taking an antibody-drug conjugate (ADC) HS630 as example.

A two-level fractional factorial design with five factors was used to investigate the effects of protein content, contents of three excipients and pH on critical quality attributes. After preparation, the samples of each group were exposed to high temperature for 28 d and light for 10 d, respectively. The contents of polymers and free DM1 were detected and analyzed.

Partial least squares (PLS) method was used for model fitting and data analysis, and the model seemed good with an acceptable predictive capability. All the excipients and pH had no significant effect on the contents of polymers and free DM1. Although it was not significant, a higher free DM1 content was noticed with higher protein content and higher pH conditions. Light and high temperature had significant effects on the attributes of drug product with a similar trend but small ranges. The formulation in the studied range was regarded as robust.

Taking MVDA method into formulation robustness study of drug products can analyze the multi-dimensional data obtained under different treatment conditions. The critical components of the formulation can be identified, and the influence of treatment conditions on the critical quality attributes can be investigated.

To establish the first batch of national reference standard of rivaroxaban.

The structure of rivaroxaban was confirmed by IR, NMR and LC-MS spectroscopy. The purity of rivaroxaban was determined by HPLC. Moreover, moisture and residual ignition were determined. The content of rivaroxaban was calculated by mass balance method.

The structure of rivaroxaban was confirmed. The content of the first batch of national reference standard of rivaroxaban was assigned as 99.6%.

The first batch of national reference standard of rivaroxaban can be applied for the identification and content determination of rivaroxaban and its related preparations.

To investigate the mechanism of compound AG-881 on inhibiting IDH1R132H mutant protein by molecular dynamics method.

The activated IDH1R132H protein structure and inactivated AG-881-IDH1R132H protein structure were constructed respectively and placed in a stereoscopic box. Molecular dynamics simulations were carried out on each system for 100 ns. The protein conformations of different systems were compared, and hydrogen bond analysis, energy analysis and principal component analysis (PCA), etc. were performed.

Substrate α-KG could stabilize IDH1R132H protein in the activated closed conformation. After AG-881 acted on the allosteric site of the protein at dimer interface, it made IDH1R132H in the open conformation of inactive state. In this process, amino acid residue Gln277 participated into the binding of AG-881. At the same time, hydrophobic occupation and hydrogen bond contributed mainly to the binding of AG-881 to IDH1R132H. In addition, halogen bond also played a certain role.

Molecular dynamics simulation can be used as an effective aid for allosteric inhibitor design, and the potential mechanism of AG-881 inhibiting IDH1R132H activity can be studied, which can further provide theoretical guidance for the development of new drugs targeting IDH1 mutant proteins.

To investigate the antibacterial effect of acetylkitasamycin dry suspension on Mycoplasma pneumoniae (MP) in vitro.

51 clinical isolates and 2 standard strains of MP from patients with respiratory tract infection stored in our laboratory from 2016 to 2019 were randomly selected for the research. Taking azithromycin and erythromycin as control drugs, the minimum inhibitory concentration (MIC) of acetylkitasamycin dry suspension against MP was determined using broth microdilution method.

Of all the 51 clinical isolates, there were 43 drug-resistant strains that contained the point mutations A2063G in V region of 23S rRNA domain, and there were 8 susceptible strains which had no mutations related to drug resistance. The MIC values of the acetyljithamycin dry suspension were 0.125 mg·L^-1 for the standard MP strains FH and M129; for the clinically resistant MP strains, the MIC was 8~32 mg·L^-1, the MIC₅₀ was 16 mg·L^-1, and the MIC₉₀ was 32 mg·L^-1; for clinically sensitive MP strains, the MIC was 0.063~0.125 mg·L^-1, and both MIC₅₀ and MIC₉₀ were 0.125 mg·L^-1. Erythromycin had a MIC range of 256~1 024 mg·L^-1 for clinically resistant MP strains, the MIC₅₀ was 512 mg·L^-1, and the MIC₉₀ was 1 024 mg·L^-1; azithromycin had a MIC range of 64~512 mg·L^-1 for clinically resistant MP strains, the MIC₅₀ was 256 mg·L^-1, and the MIC₉₀ was 512 mg·L^-1. The MIC values of erythromycin and azithromycin for clinically sensitive MP strains were <0.5 mg·L^-1.

MP showed different degrees of resistance to macrolide antibiotics. Acetylkitasamycin dry suspension had good bacteriostatic activity against sensitive MP strains in vitro, and the MIC value against resistant MP strains was low, and the clinical effect on MP infection need to be further studied.

Drug licensing transactions are constrained by many legal provisions and face many uncertainties, which confuse investors to make decisions. A reasonable risk assessment system for drug licensing transactions will help licensors grasp risks more comprehensively and carry out corresponding prevention and control.

The authors identified the risk factors through expert consultation, case analysis and other methods, and further split the risks of drug licensing transactions using the risk breakdown structure (RBS) method to obtain the risk assessment indicators of drug licensing transactions.

Eight secondary assessment indicators of drug licensing transaction risk, including strategic risk, patent and intellectual property risk, clause negotiation risk, R&D risk, cooperation risk with third parties, policy supervision risk, supply chain risk, and market risk, and 37 tertiary assessment indicators of drug licensing transaction risk were identified, and a diversified drug investment risk assessment system was constructed.

There are many complex risks in the process of drug licensing transactions. The construction of a comprehensive and reasonable drug investment risk assessment system can help investors better identify and evaluate the risks of licensing projects before making decisions.