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2026 Volume 35 Issue 9  Published: 2026-05-15
  • Tong CAI , Hua GAO , Kai-yong HE , Ran ZHU , Yu-sheng PEI
    doi: 10.20251/j.cnki.1003-3734.2026.09.001

    The bacterial endotoxin test (BET) is a key quality control method for controlling the pyrogen risk of injectable products and other sterile drugs. With the acceleration of the global integration in drug research and development, production and regulation, the harmonization of testing methods across various pharmacopoeias has become an inevitable trend. ICH Q4B guideline Annex 14 provides a harmonized assessment of the BET chapters in the United States Pharmacopeia (USP), European Pharmacopoeia (EP) and Japanese Pharmacopoeia (JP), and recommends their interchangeable use within the ICH region. The Pharmacopoeia of the People's Republic of China (ChP), as China's national drug standard, historically established its BET method based on the USP and has undergone continuous revisions to align with ICH harmonization efforts, gradually achieving international alignment. This article aims to conduct a detailed comparative analysis of the main differences between the BET in ChP 2020 edition and the ICH harmonized text, based on ICH Q4B Annex 14 and the relevant chapters of the USP, EP and JP, and to explain the background, principles, main content, and ICH Q4B harmonization considerations underlying the revision of the BET in the ChP 2025 edition. The study shows that the BET in the ChP 2025 edition further converges with the ICH harmonized text in terms of method description format, requirements for revalidation of limulus amebocyte lysate (LAL) reagents sensitivity, and certain calculation parameters. At the same time, considering China's national conditions and drug safety, it retains Chinese characteristics in aspects such as water for testing requirements, the average body weight standard for calculating endotoxin limits, gel-clot interference test, and retest requirements for the limit test. This revision reflects the ChP's principle of actively participating in international harmonization while enhancing scientific rigor and international competitiveness of standards, while also taking into account domestic regulatory practices and public health, thereby laying a more solid foundation for achieving mutual recognition in drug regulation.

  • Ying GENG , Rui DING , Ning-yi WEI , Qi-ming ZHANG , Xin-yi XU , Yue SHANG , Ping LIAO , Quan YANG , Jia-nan LIU , Ling MA , Hua CHEN
    doi: 10.20251/j.cnki.1003-3734.2026.09.002

    Weight (filling) variation is an important critical quality attribute for pharmaceutical preparations, and is one of the critical aspects for the uniformity of dosage unit testing. In the ICH tripartite pharmacopoeias (USP, EP and JP), the harmonized general chapter on uniformity of dosage units (ICH Q4B Annex 6), utilizing a unified attribute and variable sampling plan. In General Requirements for Preparations of Chinese Pharmacopoeia, the Weight (Filling) Variation test has always used an attribute sampling plan, and there are differences with the Weight (Filling) Variation test in the ICH general chapter on uniformity of dosage units in terms of the preparation scope, sampling plan, and acceptance criteria. After the harmonization process with ICH Q4B, the newly added general chapter 〈0940 Uniformity of Dosage Units〉 was incorporated in Chinese Pharmacopoeia 2025 edition. In this paper, the harmonization consideration including the preparation scope, sampling plan and acceptance criteria was reviewed and interpreted in detail for Weight (Filling) Variation test described both in 〈General Requirements for Preparations〉 and in 〈0940 Uniformity of Dosage Units〉. The harmonization with ICH can further improve China's drug regulatory capacity and facilitate drug quality control to align with international standards.

  • Ying GENG , Xiao-fen WANG , Ning-yi WEI , Qi-ming ZHANG , Xin-yi XU , Yue SHANG , Yu WU , Zi-feng ZHU , Ping LIAO , Quan YANG , Gang HOU , Tian-shou YANG , Hua CHEN
    doi: 10.20251/j.cnki.1003-3734.2026.09.003

    The disintegration test is a critical method and means for controlling the critical quality attributes of solid dosage forms. The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) harmonized the disintegration test methods of the United States Pharmacopeia (USP), European Pharmacopoeia (EP), and Japanese Pharmacopoeia (JP), resulting in the ICH Q4B Guideline Annex 5, which allows for mutual recognition within the ICH region. The 〈0921 Disintegration Test〉 in the 2025 edition of the Chinese Pharmacopoeia (ChP) has been harmonized with ICH Q4B Annex 5 (R1), achieving consistency with respect to apparatus and general procedure; acceptance criteria according to ICH and CHP are described in parallel; and the requirements for specific dosage forms as per the 2020 edition were retained. Additionally, the framework of 〈0921 Disintegration Test〉 has been revised to align with the ICH guideline, ensuring harmonization with international standards. This revision not only considers the historical inheritance of the Chinese Pharmacopoeia and the practical needs of China's pharmaceutical industry but also achieves international harmonization. This article provides a detailed comparison of the differences in apparatus and procedure between 〈0921 Disintegration Test〉 in the Chinese Pharmacopoeia and ICH Q4B Annex 5 (R1). Research on the harmonization of disintegration test methods across the ICH tripartite regions (EP, USP, JP) was carried out, including the comparison of disintegration test results, investigation of statistical data simulation for acceptance criteria, and the interpretation of the background, approach, and considerations behind the harmonization of 〈0921 Disintegration Test〉 with ICH. The aim is to enhance the understanding of the revisions to the 〈0921 Disintegration Test〉 in the 2025 edition and provide supportive reference for both the pharmaceutical industry and regulatory authorities.

  • Fang ZHANG , Tao-hua SUN , An-jin CHEN
    doi: 10.20251/j.cnki.1003-3734.2026.09.004

    Zongertinib is a novel human epidermal growth factor receptor 2 (HER2) selective tyrosine kinase inhibitor. In August 2025, zongertinib was approved by the US FDA for the treatment of adult patients with unresectable or metastatic non-squamous non-small cell lung cancer whose tumors have HER2 tyrosine kinase domain mutations and who have received prior systemic therapy. Clinical studies have shown that zongertinib has good efficacy and a manageable safety profile. Common adverse reactions of zongertinib include diarrhea, hepatotoxicity, and rash, etc.

  • Yan-ling ZHANG , Ming-shu MA , Yi-fei WANG , Rong SHAO
    doi: 10.20251/j.cnki.1003-3734.2026.09.005

    The WHO launched the regulatory system strengthening program for medical products in 2014, aiming to encourage the enhancement of medical product regulatory levels in countries and promote the coordinated development of regulatory capabilities globally. This initiative encompasses guidelines on quality management systems, good regulatory practices, good trust practices, and a global regulatory capacity framework. Its core tools are the global benchmarking tool (GBT) for regulatory system assessment and the WHO-listed authorities (WLA) framework built upon the GBT. Understanding the assessment requirements of the GBT and WLA can not only provide ideas for improving China's drug regulatory system but also serve as a reference for aligning regulatory work with international standards. This paper systematically introduces the assessment dimensions and key requirements of the GBT and WLA in order to explore their intrinsic relationship with relevant guiding principles.

  • Zi-tong LIU , Min-yu LIU
    doi: 10.20251/j.cnki.1003-3734.2026.09.006

    Patient-derived explants (PDEs) still lack a unified definition. Based on a comprehensive review of multiple studies, they are defined herein as "thin slices of tissue obtained from living tissues using tissue slicing techniques that retain cellular activity, intact tissue composition, and cellular distribution characteristics”. PDEs have been in existence for many years, but they have not yet been widely used in new drug research or clinical translational studies. Efforts to improve the culture system of PDEs and integrate more analytical techniques with the PDEs have enabled the detection of more markers using fewer tissues. As an undeconstructed ex vivo model, PDEs preserve the original tissue cell types, cellular distribution, and cellular activity and feature a high establishment rate and a short detection cycle, making them suitable for drug sensitivity testing and mechanism-related studies. In particular, they show great potential in tumour-related drug sensitivity assays and immunological studies. Therefore, PDEs represent powerful ex vivo models for disease research and new drug development.

  • Yong-xiang LIU , Xiao YE , Bin LI , Yun-li ZHAO , Ye TIAN
    doi: 10.20251/j.cnki.1003-3734.2026.09.007

    Ion chromatography, an important branch of liquid chromatography, has been widely used in the field of analytical chemistry due to its advantages including rapidity, sensitivity, good selectivity, and the ability to simultaneously determine multiple components. This paper comprehensively summarizes the technical principles, development history, detection methods and pretreatment techniques of ion chromatography (IC), with emphasis on its application in pharmaceutical analysis, particularly in the quality control of aminoglycoside antibiotics, with the aim of providing a comprehensive summary for future research and application.

  • Ya-ting DENG , Yue-chi DAI , Yan ZHAO , Jun CHANG , Yan-yan CHE , Zi-yun DUAN
    doi: 10.20251/j.cnki.1003-3734.2026.09.008

    The rapid and sustained antidepressant effects of brexanolone and zuranolone represent a breakthrough in the treatment of postpartum depression (PPD) fueling in-depth research into the antidepressant mechanisms of gamma-aminobutyric acid type A receptor (GABAAR) modulators. This article systematically reviews 14 clinical trials, and evaluates the clinical advantages and potential limitations of brexanolone and zuranolone though post-hoc analysis, providing valuable insights for clinical application. Additionally, based on recent mechanistic studies of brexanolone and its analogs, three hypotheses are proposed to explain their rapid and lasting antidepressant effects: the neuroendocrine hypothesis, neural oscillation hypothesis, and neurotrophic factor hypothesis, offering novel directions for development of drugs for PPD.

  • Ya-qin ZHEN , Xiang WANG , Ning LI , Le GAO , Li-ying NIU , Wei TIAN , Xin-guo WANG
    doi: 10.20251/j.cnki.1003-3734.2026.09.009
    Objective:

    To establish a qualitative analytical method for the chemical constituents in the root and vine of Actinidia chinensis Planch, and to systematically compare the similarities and differences between them.

    Methods:

    LC-MS was performed in negative ion mode to acquire high-resolution mass-to-charge ratios and ion intensity data of the samples from the root and vine of Actinidia chinensis Planch. Principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) were applied to the preprocessed dataset to rapidly identify differential components between the two samples.

    Results:

    The chemical compositions of root and vine were similar, primarily consisting of triterpenoids, flavonoids and phenylpropanoids, but with certain differences in content. Multivariate analysis identified 31 differential components. The root showed higher contents of triterpenoids (e.g., asiatic acid) and flavonoids (e.g., catechin) than the vine, while five differential compounds, including fraxin and aesculetin, were relatively more abundant in the vine.

    Conclusion:

    This study clarifies the similarities and differences in chemical composition between the root and vine of Actinidia chinensis Planch. The admixture of vine into the root was found to compromise its quality. This study provides significant implications for ensuring the quality of root of Actinidia chinensis Planch., guiding clinical medication, and facilitating the medicinal development of both root and vine resources.

  • Xiang-hui MENG , Jia-bei SUN , Yu WANG , Shang-chen YAO
    doi: 10.20251/j.cnki.1003-3734.2026.09.010
    Objective:

    To establish a supercritical fluid chromatography (SFC) method for the determination of chiral purity of palonosetron hydrochloride using two columns in series, and to determine the isomers in palonosetron hydrochloride bulk drug and injections.

    Methods:

    Two columns, DAICEL CHIRALPAK AD-3 (150 mm×3.0 mm, SFC, 3 μm) and DAICEL CHIRALPAK IG-3 (150 mm×3.0 mm, SFC, 3 μm), were in series. The column temperature was at 37 ℃, the mobile phase was composed of CO2 and a mixture of anhydrous ethanol, acetonitrile, and diethylamine at a ratio of 55∶45, the back pressure was at 12 MPa, the flow rate was 1.2 mL·min-1, the injection volume was 20 μL, and the detection wavelength was at 240 nm.

    Results:

    The R,S isomer, R,R enantiomer, S,R isomer, and palonosetron were eluted sequentially within 10 min with resolutions of 1.7, 2.3, and 1.5, respectively. All four compounds exhibited good linearity between peak area and concentration in the range from 0.20 to 10.0 μg·mL-1, with r all greater than 0.999 5. The detection limits (S/N=3) of the three isomers were all 0.10 μg·mL-1; and the quantitation limits (S/N=10) were all 0.20 μg·mL-1. The average recoveries of the three isomers in the bulk drug and injections ranged from 97.8% to 101.3%, with relative standard deviations (RSDs) ranged from 0.3% to 1.5% (n=9). Except for one batch of bulk drug in which no chiral impurity was detected, the R,S isomer was detected in all the other five batches, with contents ranging from 0.03% to 0.12%.

    Conclusion:

    The developed SFC method can separate palonosetron and its three isomers in a short analysis time, and the use of two columns in series improves the separation efficiency, especially the resolution between the S,R isomer and palonosetron. The method is accurate, reliable, and can be used as an effective means for chiral purity determination and quality control of palonosetron hydrochloride bulk drug and related preparations.

  • Jie LI , Song YUAN , Lei-jin ZHU , Yang LIU
    doi: 10.20251/j.cnki.1003-3734.2026.09.011
    Objective:

    To study the impurities in domestic piroxicam gel.

    Methods:

    An HPLC method was established to study the impurities in piroxican gel. Waters XBridge C18 (250 mm×4.6 mm, 5 μm) column was used with gradient elution of mobile phase consisting of 0.5% of glacial acetic acid in water (adjust with ammonium hydroxide to a pH of 6.2) and acetonitrile. The flow rate was 1.0 mL·min-1, and the UV detection wavelength was 265 nm. Q-TOF technique was used to identify the structures of the main impurities in positive/negative ion modes with ESI as the ion resource.

    Results:

    Piroxicam peak was well separated from each impurity peak. A total of 4 major impurities (≥0.1%) were detected in 17 batches of domestic piroxicam gel: i.e., 2-hydroxy-benzoic acid 2-[bis(2-hydroxyethyl)amino] ethyl ester, 2-hydroxypropyl-4-hydroxybenzoate, 1-hydroxypropyl-2-yl-4-hydroxybenzoate, and 2-methyl-4-methoxy-N-(2-pyridyl)-2H-1,2-benzothiazin-3-formamide-1,1-dioxide, which were for the first time reported in piroxicam gel.

    Conclusion:

    The established HPLC method can be used for impurity detection of piroxicam gel. Impurities in domestic piroxicam gel mainly come from raw materials and excipient ethyl hydroxybenzoate. The production process should be optimized to improve the quality.

  • Chen PAN , Xiao-dong LIU , Yong-qi XIE , Yi WU , Ran-jia LIU , Zhen-huan WANG , Xiang-li CUI
    doi: 10.20251/j.cnki.1003-3734.2026.09.012
    Objective:

    To analyze the rationality and effectiveness of hepatoprotective drugs in clinical practice and explore the evidence-based basis for off-label use, as well as the clinical value of prophylactic use and combination therapies.

    Methods:

    Clinical data of 732 hospitalized patients treated with hepatoprotective drugs from January 2023 to December 2024 were collected. Rationality was evaluated based on drug labels, domestic and international guidelines, and expert consensus. Effectiveness was assessed by comparing liver function indicators before and after treatment.

    Results:

    A total of 732 patients were included. Rational use of hepatoprotective drugs was observed in 592 cases (80.87%), while 140 cases (19.12%) were categorized as irrational use. Rational use was subcategorized into label-compliant use (252 cases, 34.43%) and off-label use (340 cases, 46.45%). Off-label use cases were further classified as guideline-supported (91 cases, 12.43%) and consensus-supported (249 cases, 34.02%). Irrational use primarily included non-indicated prescriptions (58 cases, 7.92%), prophylactic use (43 cases, 5.87%), and redundant combinations (20 cases, 2.73%). Significant reduction in alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (TBIL) levels was observed after treatment (all P<0.001). The effective rate was significantly higher in the label-compliant group than in the inappropriate-use group (72.62% vs 53.57%, P<0.05). No statistically significant differences were found among monotherapy, dual therapy, and triple-or-more therapy groups (62.54% vs 69.31% vs 62.79%, P>0.05).

    Conclusion:

    Clinical application of hepatoprotective drugs should strictly adhere to instructions and authoritative guidelines, and avoid non-indicated prescriptions or combination therapy. This study provides a reference for rational clinical medication use and clinical pharmacist interventions.

  • Yu-xi ZHANG , Ran-ran ZHANG , Jing ZHANG , Sheng-nan GAO , Ning GAO , Bing FENG , Ran LIU , Guo-qiang LIU
    doi: 10.20251/j.cnki.1003-3734.2026.09.013
    Objective:

    To evaluate the cost-effectiveness of imipenem/cilastatin/relebactam (IMI/REL) in patients with hospital-acquired bacterial pneumonia (HABP) and ventilator-associated pneumonia (VAP), using piperacillin/tazobactam (PIP/TAZ) as a comparator, and to assess its economic viability within the Chinese healthcare system.

    Methods:

    From the perspective of the Chinese healthcare system, a hybrid decision tree-Markov model was constructed to simulate the long-term health outcomes of IMI/REL and PIP/TAZ from the mean age of disease onset until death. Efficacy and safety data were derived from a Phase Ⅲ clinical trial (NCT03583333), while cost and utility parameters were obtained based on literature reviews and expert interviews. Cost-utility analysis was performed, and one-way and probabilistic sensitivity analyses were conducted to validate the robustness of the results. The unit price of IMI/REL was set at 1 240 yuan per vial based on publicly available sales prices, and which both base-case and scenario analyses were conducted.

    Results:

    The base-case analysis showed that the total treatment cost in the IMI/REL group was 164 275.71 yuan with a quality-adjusted life year (QALY) of 4.32, while the total cost in the PIP/TAZ group was 143 946 yuan with a QALY of 4.13. The incremental cost-utility ratio (ICER) was 104 991.37 yuan per QALY, which was lower than the threshold of three times China's per capita gross domestic product (GDP). The scenario analysis indicated that under the assumption of partial survival among uncured patients, the cost-effectiveness conclusion of IMI/REL remained robust.

    Conclusion:

    Under the currently available price setting, IMI/REL demonstrates favorable cost-effectiveness compared with PIP/TAZ, providing a reference for optimizing treatment strategies and informing medical insurance payment policies for HABP/VAP in China.

  • Qiu-ya YANG , Xia LIU
    doi: 10.20251/j.cnki.1003-3734.2026.09.014
    Objective:

    To investigate the relationship between potentially inappropriate medication (PIM) and falls among the elderly in the medical-nursing integration community, and to provide a basis for fall prevention in the elderly.

    Methods:

    A retrospective study was conducted. General information of the participants was collected, including basic information, disease conditions, medication use, various assessment records, and records of fall events. PIM screening was performed using the criteria of potentially inappropriate medications for older adults in China (2017). Statistical analyses were performed using R 4.3.0. Depending on the data type, t-tests, non-parametric rank sum test, or chi-square test was used, and logistic regression was used to analyze the relationship between various risk factors and falls.

    Results:

    A total of 1 153 elderly individuals from the medical-nursing integration community were enralled and divided into two groups based on the presence of falls between January 2022 and June 2024: the fall group (n=290) and the non-fall group (n=863). Multivariate Logistic regression analysis showed that increased age, the presence of pain, anxiety and depression, and an increased number of psychotropic PIMs, endocrine PIMs, and NSAID PIMs were independent risk factors for falls (P<0.05), whereas a higher education level was a protective factor against falls (P<0.05).

    Conclusion:

    An increased number of endocrine PIMs, NSAID PIMs, and psychotropic PIMs is closely associated with falls in the elderly. Clinicians should promote rational drug use, reduce the types and numbers of PIMs, and thus lower the risk of falls in this population.