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We established a strategy integrating chemical analysis, network pharmacology, and multi\u2010compartment transdermal pharmacokinetics. Comprehensive chemical profiling by UPLC\u2010Q\u2010TOF\u2010MS identified 100 constituents. Network pharmacology screened 15 core bioactive components. A validated UPLC\u2010QqQ\u2010MS\/MS method was developed to simultaneously quantify eight components in the stratum corneum (SC) and viable epidermis plus dermis (VD) and four systemically absorbed components in plasma after transdermal administration, elucidating the formulation's in\u00a0vivo behavior. Pharmacokinetics revealed structure\u2010dependent transdermal patterns: Phenylpropanoids and phthalides showed rapid absorption and elimination, while organic acids, alkaloids, and flavonoids exhibited reservoir effects and slow release in the SC, contributing to a \u201cfast\u2010slow synergistic\u201d mechanism. Given its high transdermal permeability, notable local and systemic exposure, and established anti\u2010inflammatory evidence, ferulic acid is proposed as a potential quality marker for CNZP. This study provides evidence for the in\u00a0vivo behavior of topical Chinese medicines and suggests methods for quality control and active substance research.<\/jats:p>","DOI":"10.1002\/bmc.70395","type":"journal-article","created":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T09:54:44Z","timestamp":1770890084000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Unraveling the Material Basis of Compound Nanxing Zhitong Plaster: A Multimodal Study Combining Chemical Analysis, Network Pharmacology, and Transdermal Pharmacokinetics"],"prefix":"10.1002","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-5562-0681","authenticated-orcid":false,"given":"Ni","family":"Yan","sequence":"first","affiliation":[{"name":"Jiangsu Provincial Engineering Research Center of TCM External Medication Development and Application Nanjing University of Chinese Medicine  Nanjing China"},{"name":"School of Pharmacy Nanjing University of Chinese Medicine  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aomin","family":"Zhou","sequence":"additional","affiliation":[{"name":"Jiangsu Provincial Engineering Research Center of TCM External Medication Development and Application Nanjing University of Chinese Medicine  Nanjing China"},{"name":"School of Pharmacy Nanjing University of Chinese Medicine  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong","family":"Tian","sequence":"additional","affiliation":[{"name":"Jiangsu Provincial Engineering Research Center of TCM External Medication Development and Application Nanjing University of Chinese Medicine  Nanjing China"},{"name":"School of Pharmacy Nanjing University of Chinese Medicine  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Dong","sequence":"additional","affiliation":[{"name":"Jiangsu Provincial Engineering Research Center of TCM External Medication Development and Application Nanjing University of Chinese Medicine  Nanjing China"},{"name":"School of Pharmacy Nanjing University of Chinese Medicine  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7198-1844","authenticated-orcid":false,"given":"Shaoping","family":"Yin","sequence":"additional","affiliation":[{"name":"Jiangsu Provincial Engineering Research Center of TCM External Medication Development and Application Nanjing University of Chinese Medicine  Nanjing China"},{"name":"School of Pharmacy Nanjing University of Chinese Medicine  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9241-2683","authenticated-orcid":false,"given":"Jun","family":"Chen","sequence":"additional","affiliation":[{"name":"Jiangsu Provincial Engineering Research Center of TCM External Medication Development and Application Nanjing University of Chinese Medicine  Nanjing China"},{"name":"School of Pharmacy Nanjing University of Chinese Medicine  Nanjing China"},{"name":"Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization Nanjing University of Chinese Medicine  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,2,12]]},"reference":[{"issue":"4","key":"e_1_2_11_2_1","first-page":"283","article-title":"Combined Use of Compound Nanxing Pain Paste With Blood\u2010Promoting and Diuretic Chinese Herbal Medicines in Treatment of Chronic Knee Synovitis","volume":"25","author":"Chen S. 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