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• 2026 Volume 57 Issue 5
  Published: 10 May 2026

    

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Perspective & Review
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  Perspective & Review

  Research Progress of Nanodelivery Systems for siRNA Drugs in Lung-targeted Therapy of Respiratory Diseases

  WANG Jiahui, GU Fenghua

  2026, 57(5): 499. https://doi.org/10.16522/j.cnki.cjph.2026.05.001

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  Small interfering RNA(siRNA) is a programmable gene-silencing therapeutic agent that can specifically downregulate the expression of pathogenic genes through the RNA interference mechanism, thereby exhibiting significant potential in precision therapy for respiratory diseases. In recent years, siRNA agents targeting key pathogenic genes in respiratory diseases have shown promising therapeutic efficacy in disease models such as lung cancer, asthma, COPD, and idiopathic pulmonary fibrosis. However, naked siRNA suffers from several limitations, including poor in vivo stability, high susceptibility to nuclease degradation, low transmembrane delivery efficiency, difficulty in penetrating the pulmonary mucus barrier, and inadequate endosomal escape capability, which severely hinder its clinical translation. To address these challenges, various nanoscale delivery systems, including lipid nanoparticles, polymeric nanoparticles, viral vectors, inorganic nanomaterials, and exosomes, have been developed for the efficient delivery of siRNA to pulmonary lesions. Centered on the “disease - siRNA target - delivery system” framework, this review systematically summarizes the research progress of representative siRNA-based nanoscale delivery systems for respiratory diseases. It critically examines how different nanocarriers influence siRNA delivery efficiency with respect to systemic circulation stability, pulmonary targeting, mucus penetration, cellular uptake, and endosomal escape. Furthermore, it outlines optimization strategies such as passive targeting, ligand modification, stimuli-responsiveness, and biomimetic modification, aiming to provide a reference for further research and clinical translation of siRNA therapeutics for lung-targeted treatment of respiratory diseases.
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  Perspective & Review

  Research Progress on Polysorbate-degrading Enzymes in Recombinant Protein Therapeutics and Related Detection Technologies

  LI Jiahui, HU Zhishang, ZHANG Yafen

  2026, 57(5): 508. https://doi.org/10.16522/j.cnki.cjph.2026.05.002

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  Polysorbate-degrading enzymes(PSDE) are endogenous protein mixtures secreted by host cell lines during the manufacture of recombinant protein drugs and are unrelated to target products. PSDE degrade common excipients(such as polysorbate 20 and polysorbate 80) in protein formulations, thereby generating fatty acid particles, protein particles, and composite particles, further compromising product safety and reducing shelf-life stability. The detection and quantitative analysis of PSDE are critical steps to ensure drug safety. ELISA and MS are commonly used for PSDE detection. This article reviews the principles of enzymatic hydrolysis of excipients, the classification of PSDE, and commonly used detection methods. It highlights that the development of reference materials is critical for quantitative analysis, providing reference and guidance for subsequent PSDE detection.
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  Paper

  Improved Synthetic Process of Elacestrant

  LUO Kun, LIU Xuyan, ZHANG Tengda, FAN Xiaonan, WANG Guan,

  2026, 57(5): 516. https://doi.org/10.16522/j.cnki.cjph.2026.05.003

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  This study focuses on the synthetic process optimization of elacestrant(1). Starting from 7-benzyloxy- 3-bromo-1,2-dihydronaphthalene(2), a one-pot sequence involving the Miyaura reaction and Suzuki cross-coupling reaction with 2-bromo-5-methoxyacetanilide(4) afforded N-[2-[6-(benzyloxy)-3,4-dihydronaphthalen-2-yl]-5methoxyphenyl]- acetamide(5). Compound 5 was reduced with hydrogen under the catalysis of palladium hydroxide on carbon to yield the racemic N-[2-(6-hydroxy-1,2,3,4-tetrahydronaphthalen-2-yl)-5-methoxyphenyl]acetamide(6). Compound 6 underwent deacetylation to yield the racemic compound 6-(2-amino-4-methoxyphenyl)-5,6,7,8-tetrahydronaphthalen-2-ol(7). Resolution of 7 with L-(–)-dibenzoyl tartaric acid, followed by further resolution with D-(+)-dibenzoyl tartaric acid and basification, furnished (R)-6-(2-amino-4-methoxyphenyl)-5,6,7,8-tetrahydronaphthalen-2-ol[(R)-7]. Reductive amination of (R)-7 with N-ethyl-2-(4-formylphenyl)acetamide(8) produced N-ethyl-4-[[ethyl[5-methoxy-2-[(2R)- 1,2,3,4-tetrahydro-6-hydroxy-2-naphthalenyl]phenyl]amino]methyl]benzeneacetamide[(R)-9]. Finally, reduction under sodium borohydride/iodine conditions and subsequent salt formation yielded the target product 1. The overall yield was approximately 18％ (based on 2), with chemical purity over 99.7％ and ee value over 99.99％ . This process features mild reaction conditions and stable, controllable product quality.
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  Synthesis of the Key Intermediate of Darunavir Named (3aS,6aR)-9-cis-Tetrahydro-4- methoxyfuro[3,4-b]furan-2(3H)-one

  LONG Zhongzhu, LI Linwang, CHEN Yong, TENG Dawei, CAI Shuihong

  2026, 57(5): 522. https://doi.org/10.16522/j.cnki.cjph.2026.05.004

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  The synthetic process of (3aS,6aR)-9-cis-tetrahydro-4-methoxyfuro[3,4-b]furan-2(3H)-one(1), a key intermediate of an anti-AIDS drug darunavir, was investigated. Compound 5,6-O-isopropylidene-L-ascorbic acid(3) was prepared from L-ascorbic acid(2) via ketalization, which was then subjected to one pot reaction(including hydrogen peroxide oxidation, sodium hypochlorite oxidation and Wittig-Horner reaction) to obtain methyl (R,E)-3-(2,2-dimethyl- 1,3-dioxolan-4-yl)acrylate(6). After experiencing Michael reaction, Nef reaction and cyclization, the key intermediate of darunavir 1 was obtained with the overall yield of 26.7％(based on 2), with the purity of 99.1％ and chiral purity of 99.8 ％ . This synthetic process avoids the hardening of mineral salt on the production device, which is simple to operate with low cost and easy to scale up for industrial production.
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  Design, Synthesis and Anti-inflammatory Activities of Matrine Derivatives

  YANG Qianling, SONG Jia, SHEN Hongxia, CHAI Xiaoyun, ZHAO Qingjie,

  2026, 57(5): 527. https://doi.org/10.16522/j.cnki.cjph.2026.05.005

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  A series of matrine(1) derivatives were designed and synthesized. Based on the tetracyclic rigid scaffold of 1 as the parent core, structural modifications were carried out by introducing a thione group at the C15 position and installing substituted cinnamamidomethyl or heteroaromatic amidomethyl groups at the C13 position. This strategy yielded twelve novel derivatives(B1 - B9 and E1 - E3), whose structures were fully characterized by ¹H NMR, ¹³C NMR, and HRMS. The anti-inflammatory activities of these compounds were evaluated in lipopolysaccharide-induced RAW264.7 macrophage cells. At a concentration of 12.5 μmol/L, all derivatives inhibited nitric oxide(NO) production more effectively than the parent compound 1[(41.15±0.23)％ ]. Notably, compounds B1 - B3 exhibited superior inhibitory activities[(70.40±0.83) ％ , (71.10±0.69) ％ and (71.89±0.71) ％ , respectively]), outperforming the reported positive control 13-methylamino-18-thiomatrine[(64.68±0.39)％ ]. Structure-activity relationship analysis suggested that introducing a substituted cinnamamidomethyl moiety at C13 enhanced anti-inflammatory potency. Among them, compound B3 demonstrated strong inhibitory effects on key inflammatory mediators, including NO, IL-6, and TNF-α, indicating its potential as a promising anti-inflammatory lead compound for further development.
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  Paper

  An Efficient Escherichia coli Production Process for the Fc Variant Fc3

  LIN Shuqi, WANG Yapeng, HUA Haoju, LU Jianguang, FENG Jun,

  2026, 57(5): 537. https://doi.org/10.16522/j.cnki.cjph.2026.05.006

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  The preparation of antibody crystallizable fragment(Fc) often relies on costly mammalian cell expression systems, and its complement dependent cytotoxicity(CDC) and antibody-dependent cell-mediated cytotoxicity(ADCC) pose potential safety risks. To address these bottlenecks, this study efficiently produced the Fc variant Fc3(1) in Escherichia coli. This variant exhibits weaker CDC and ADCC effects and reduced hinge region disulfide bonds through amino acid mutations, which is conducive to industrial production. This study systematically optimized process parameters, achieving efficient refolding and separation and purification of 1, with a yield of 407.4 mg/L and a purity of 91.2％ . Subsequently, the equilibrium dissociation constant(KD) of 1 binding to neonatal Fc receptor(FcRn) at pH 6.0 was measured to be 10.8 nmol/L using bio-layer interferometry, while the binding was very weak at pH 7.4, demonstrating successful expression of 1 in E. coli and its typical pH-dependent FcRn binding characteristics. This study provides a feasible technical pathway for the low-cost, high-yield production of Fc-like proteins and lays the foundation for the subsequent application of 1.
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  Preparation of VEGFA/B Antagonistic Supramolecular Peptides and Their Application in the Treatment of Melanoma in Mice

  ZHANG Qian, LIU Wenqi, FANG Yuelin, ZHANG Xinxin,

  2026, 57(5): 546. https://doi.org/10.16522/j.cnki.cjph.2026.05.007

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  Peptide drugs occupy a unique position in the field of tumor therapy due to their high specificity and potent activity. However, their clinical translation and application are often restricted by poor stability and low cellular uptake efficiency. To address this, this study employed the vascular endothelial growth factor A/B antagonistic peptide VGB3 as the model drug, and screened amphiphilic molecules bearing ion-pair structures in combination with salt ions to drive the preparation of VGB3 supramolecular peptide(V-SMP). The average particle size of V-SMP was approximately 150 nm, and it appeared as monodisperse regular spherical particles under a transmission electron microscope and exhibited good stability. Cell experiment results showed that V-SMP increased the uptake efficiency of VGB3 in mouse melanoma cells(B16F10 cells) by 1.49-fold and effectively inhibited tumor cell proliferation. In a subcutaneous syngeneic model of B16F10 melanoma, V-SMP significantly inhibited tumor growth, achieving antitumor efficacy nearly twice that of the free peptide. In summary, this supramolecular peptide formulation improves both the stability and therapeutic activity of peptide drugs, providing a valuable reference for tumor therapy and peptide drug development.
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  Formulation Optimization and in vitro Release Mechanism of Ketorolac Tromethamine Ion-sensitive Ophthalmic in situ Gels

  YUAN Yue, ZHU Chunmei, SHI Limin, YANG Chuanji, ZHANG Fuli, WU Haoxiang

  2026, 57(5): 557. https://doi.org/10.16522/j.cnki.cjph.2026.05.008

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  In this study, gellan gum(GG) and hydroxyethyl cellulose(HEC) were used as the composite matrix. With the formulation viscosity at 25 ℃ and the gel viscosity after mixing with simulated tear fluid at 34 ℃ as the response indicators, a central composite design-response surface methodology was adopted to optimize the formulation of ketorolac tromethamine ion-sensitive in situ ophthalmic gels. The final optimized formulation consisted of 0.53％ GG and 0.11％ HEC. Subsequently, an in vitro release assay based on UV spectrophotometry was established and validated, and the release behavior was evaluated using a modified paddle method. The in situ gels prepared with the optimized formulation achieved a cumulative release rate of over 90％ within 8 h, significantly prolonging the drug release time. The release kinetics conformed to the Ritger-Peppas model(Q=5.257 0t0.459 8, R2=0.984 3), indicating that the release mechanism was predominantly Fickian diffusion. The results indicated that the ion-sensitive ophthalmic in situ gels exhibited excellent performance and held promise for improving ocular bioavailability by prolonging corneal retention time.
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  Preparation and Performance Evaluation of a Highly Stable Flurbiprofen Patch

  HUANG Xiaolong, HU Yanping, LIU Qian, LIU Zixiu, PAN Lin

  2026, 57(5): 562. https://doi.org/10.16522/j.cnki.cjph.2026.05.000

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  To address the issue of flurbiprofen menthyl ester impurity formation during long-term storage of flurbiprofen(1) patches, this study prepared 1 patches using maleic anhydride-grafted styrene-isoprene-styrene block copolymer(SIS-MAH) as the matrix skeleton. The formulation was systematically optimized via a Box-Behnken design, with adhesion and in vitro release performance as evaluation indicators. The final optimized formulation was as follows: SIS-MAH of 27.5％ , high molecular weight polyisobutylene of 4.96％ , low molecular weight polyisobutylene of 6.04％ , liquid paraffin of 44.20％ , hydrogenated rosin glycerin ester of 11.74％ , L-menthol of 2.38％ , zinc stearate of 0.5％ , and butylated hydroxytoluene of 0.3％ . The optimized 1 patches showed key quality attributes comparable to those of the reference listed drug, including drug release behavior, skin permeation performance, and skin adhesion. Preliminary stability test results indicated that the self-developed 1 patches exhibited significant advantages in long-term stability and impurity control, with a markedly lower flurbiprofen menthyl ester content than that of the reference listed drug, demonstrating high safety for clinical application.
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  Extraction of Polygonatum kingianum Polysaccharides and Their Protective Effect against Ethanol-induced Oxidative Stress Injury on Rat Liver

  LI Xueling, LI Xi, ZHAO Runlan, YAN Yun, ZHANG Min, XU Yuannan

  2026, 57(5): 570. https://doi.org/10.16522/j.cnki.cjph.2026.05.010

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  The complex enzymatic hydrolysis was adopted to extract Polygonatum kingianum polysaccharides(PKP), and the enzymolysis and extraction process parameters were optimized. The optimized parameters were determined as follows: cellulase, pectinase and alkaline protease adding amounts of 2.6 ％ , papain of 2.0 ％ , solidliquid ratio of 1 ∶ 60, enzymolytic pH value of 5.0, and extraction temperature of 50 ℃ . In vitro antioxidant tests showed that the 1,1-diphenyl-2-picrylhydrazyl free radical scavenging rate of 8.00 mg/mL PKP solution reached 92.19 ％ , and the hydroxyl free radical scavenging rate of 5.00 mg/mL PKP solution was up to 98.18％ . However, the total reducing capacity of PKP was still inferior to that of vitamin C. With bifendate dropping pills(4 mg/kg) as the positive control, in vivo experiments verified that high and low doses(490 and 245 mg/kg) of PKP could prevent ethanol-induced oxidative stress damage in the liver of rats. Compared with the model group, the activities of alcohol dehydrogenase and aldehyde dehydrogenase in the liver and serum of rats in the PKP intervention groups were enhanced, the serum ethanol content was reduced, and the levels of alanine amino-transferase, glutamic-oxaloacetic transaminase and alkaline phosphatase in serum were significantly decreased. Moreover, PKP markedly up-regulated the activities of superoxide dismutase, catalase and glutathione peroxidase in rat serum and liver, and down-regulated the malondialdehyde content. This study demonstrates that the mechanism of PKP is closely related to promoting alcohol metabolism and relieving oxidative stress, which provides a theoretical basis for the prevention of alcoholic liver disease.
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  Simultaneous Determination of 11 Components in Luohua Zizhu Granules by UPLCMS/ MS and Preliminary Investigation of Protective Efficacy of Composition on Ulcerative Colitis

  LIU Mo, OUYANG Danwei, KANG Xingdong, WU Tong

  2026, 57(5): 578. https://doi.org/10.16522/j.cnki.cjph.2026.05.011

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  A straightforward and swift UPLC-MS/MS method was established for simultaneous determination of 11 compounds in Luohua Zizhu granules, including geniposidic acid, decaffeoylacteoside, cistanoside F, protocatechualdehyde, caffeic acid, ferulic acid, luteoloside, acteoside, isoacteoside, 2'-acetylacteoside, luteolin. The combination of these components was prepared according to their measured contents, and its protective effect against ulcerative colitis was investigated. The analysis was performed on a Waters ACQUITY UPLC BEH C18 column(2.1 mm× 150 mm, 1.7 μm). Gradient elution was conducted using. 0.1％ formic acid aqueous solution as mobile phase A and 0.1％ formic acid in acetonitrile as mobile phase B. The flow rate was 0.35 mL/min, and the column temperature was maintained at 35 ℃ . A mouse model of acute ulcerative colitis induced by dextran sulfate sodium was established to evaluate the protective effect of the 11-component combination from Luohua Zizhu granules. The 11 components showed good linear relationships between peak area and mass concentration within their respective ranges(r2>0.999). The average spiked recovery rates were 97.58 ％ - 104.10 ％ , with RSDs of 1.29 ％ - 2.77 ％ . Compared with the model group, the disease activity index of mice in the treatment group was significantly reduced(P<0.05), the colon length of mice was markedly prolonged(P<0.01), and colonic pathological injury was alleviated. Meanwhile, the expression levels of inflammatory factors TNF-α and IL-1β in the colon was significantly decreased(P<0.05), while the expression level of IL-10 in the colon was significantly increased(P<0.05). This method is accurate, reliable, sensitive and rapid, which can provide an experimental basis for the quality control and clinical application of Luohua Zizhu granules.
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  Determination of Mirogabalin in Rat Plasma by UPLC-MS/MS and Pharmacokinetic Study

  LI Linshuo, WANG Rui, WANG Xiaosu, LIU Yang, ZHANG Tao,

  2026, 57(5): 585. https://doi.org/10.16522/j.cnki.cjph.2026.05.012

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  A UPLC-MS/MS method was developed and validated for the determination of mirogabalin in rat plasma. Detection was carried out by electrospray ionization in positive ion mode with multiple reaction monitoring. Chromatographic separation was performed on an XBridge C18 column(4.6 mm×75 mm, 3.5 μm) with the mobile phase consisting of 0.1％ formic acid aqueous solution and acetonitrile in gradient elution mode at a flow rate of 0.6 mL/min. Plasma samples were pretreated by acetonitrile protein precipitation with tolbutamide as the internal standard. The assay exhibited good linearity over the concentration range of 0.5 - 600.0 ng/mL, with a lower limit of quantitation of 0.5 ng/mL. Intra- and inter-day RSDs were less than 10％ . The extraction recovery, matrix effect, stability, and dilution integrity all met the requirements for bioanalytical method validation. This simple, sensitive, and reliable method is suitable for the determination of mirogabalin in rat plasma and can be used for pharmacokinetic studies.
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  Analysis of Volatile Component Differences in Different Processed Products of Cuscutae Semen by HS-GC-IMS Combined with Chemometrics

  SONG Yijun, GUO Tao, FENG Yuxin, CHEN Tianle, ZHANG Shimao

  2026, 57(5): 590. https://doi.org/10.16522/j.cnki.cjph.2026.05.013

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  A headspace-gas chromatography-ion mobility spectrometry(HS-GC-IMS)was used to detect the volatile components of four different processed products of Cuscutae Semen, namely raw Cuscutae Semen, stir-baked Cuscutae Semen, Cuscutae Semen stir-baked with salt-water and Cuscutae Semen cakes stir-baked with wine. A total of 127 characteristic signals of volatile components were detected in the processed products, among which 89 components were qualitatively identified, including 27 aldehydes, 19 ketones, 17 alcohols, 13 esters, 3 acids, 3 pyrazines, 2 monoterpenes, 2 sulfides, 1 pinene derivative, 1 furan derivative, and 1 pyrrole derivative. Chemometric methods including principal component analysis, orthogonal partial least squares-discriminant analysis, and cluster analysis were used to visualize the differences in volatile components among the different processed products. The results of the cluster heatmap showed that 34 characteristic volatile components, including pyrrole, acetic acid dimer, and hydroxyacetone dimer, could be used as discriminative markers for distinguishing different processed products of Cuscutae Semen. The results of this study can provide a scientific basis for the identification of different processed products of Cuscutae Semen, and offer references for the quality control and clinical application of Cuscutae Semen decoction pieces.
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  Establishment and Validation of an ELISA Method for Host Cell Protein Residues in Drug Substance of Recombinant Human Hepatocyte Growth Factor Naked Plasmid Injection

  ZHANG Bo#, WANG Yinuo#, MA Shanshan, LI Shangru, HOU Huili

  2026, 57(5): 602. https://doi.org/10.16522/j.cnki.cjph.2026.05.014

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  Recombinant human hepatocyte growth factor naked plasmid injection is produced using an Escherichia coli expression system, which may lead to residual E. coli host cell protein(HCP) during manufacturing. A double-antibody sandwich ELISA method was established for determination of HCP residues in the drug substance of recombinant human hepatocyte growth factor naked plasmid injection. The results showed that the drug substance required no dilution for testing and no interference was observed in the detection of E. coli HCP indicating good specificity. The E. coli HCP standard showed a good linear relationship with the four-parameter logistic curve of OD₄₅₀ values in the mass concentration range of 3 - 200 ng/mL(R²>0.999), with a LOQ of 3 ng/mL. The recoveries ranged from 93.0％ to 100.2％ , with RSD between 3.3％ and 6.3％ . The repeatability RSD was 12.1％ , and the intermediate precision RSD was 11.6％ . The HCP residues in three batches of drug substance were all below the specification of 1 μg/mg plasmid. This method may serve as a reference for the determination of HCP residues in similar products and other recombinant biologics produced by E. coli fermentation processes.
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  HPLC Determination of Five Peroxides Extracted from Silicone Rubber Production Pipelines

  LIU Yuan

  2026, 57(5): 607. https://doi.org/10.16522/j.cnki.cjph.2026.05.015

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  An HPLC method was established for the determination of five peroxides[di-tert-butyl peroxide, dicumyl peroxide, bis[1-(tert-butylperoxy)-1-methylethyl]benzene, 2,5-dimethyl-2,5-di(tert-butylperoxy)hexane and benzoyl peroxide] in different extraction media from silicone rubber production pipelines. A Poroshell 120 EC-C18 column(4.6 mm×50 mm, 2.7 μm) was used. Separation was performed using a water‑acetonitrile‑propanol gradient at a flow rate of 1 mL/min. The detection wavelength was 254 nm and column temperature was 35 ℃ .The silicone rubber tubes were extracted with three extraction media(pH 2.5 medium, pH 12.0 mediumand and 50％ ethanol). The extracts were then subjected to analysis. di-tert-Butyl peroxide, dicumyl peroxide, bis[1-(tert-butylperoxy)-1-methylethyl]benzene and 2,5-dimethyl-2,5-di(tert-butylperoxy)hexane showed good linear relationships within the corresponding mass concentration ranges, with extraction recoveries of 76.5 ％ - 103.7 ％ . The extraction recovery of benzoyl peroxide was low in three media. This method can provide a reference for the quality control of five peroxides in silicone rubber production pipelines.
Pharmaceutical Management & Information
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  Pharmaceutical Management & Information

  Thoughts on the Application of Real-world Data in Regulatory Decision-making for Pediatric Drug Development

  LING Xing, HE Jie, GUO Wen,

  2026, 57(5): 612. https://doi.org/10.16522/j.cnki.cjph.2026.05.016

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  Pharmaceutical Management & Information

  Quantitative Research on the Influencing Factors of Industry Concentration in the Pharmaceutical Industry under the Background of Centralized Procurement

  WANG Miao, WANG Xutao, YAO Yan, SU Hong

  2026, 57(5): 619. https://doi.org/10.16522/j.cnki.cjph.2026.05.017

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