{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T15:03:24Z","timestamp":1781795004727,"version":"3.54.5"},"reference-count":35,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2025,11,14]],"date-time":"2025-11-14T00:00:00Z","timestamp":1763078400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82274091"],"award-info":[{"award-number":["82274091"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Gastrodiae Rhizoma (GR) is known to have a medicinal and food-based homology. It is used to treat infantile convulsion, epilepsy, spasm, tetanus, and vertigo. In this study, an ultra-high performance liquid chromatography\/tandem mass spectrometry (UHPLC-MS\/MS) method was developed and validated to quantify fourteen components (p-hydroxybenzyl alcohol, gastrodin, parishin E, p-hydroxybenzoic acid, parishin C, parishin A, parishin B, nicotinamide, p-hydroxybenzaldehyde, adenosine, 3,4-dihydroxybenzaldehyde, syringaldehyde, dauricine, and nobiletin) of GR in rat plasma. Methanol precipitation was used to prepare the samples with astragalin, serving as the internal standard. In multiple reaction monitoring (MRM) mode, the fourteen components were separated by gradient elution on a Waters ACQUITY UPLC\u00ae HSS T3 column. Under these conditions, all fourteen analytes\u2019 calibration curves demonstrated strong linearity within wide concentration ranges (r &gt; 0.9941). Accuracy for the intra-day and inter-day assessments ranged from \u221213.74% to 12.76%, and the precision for all analytes remained below 8.88%. The analytes\u2019 extraction recoveries ranged from 66.78% to 114.2%, accompanied by matrix effects ranging from 63.65% to 117.61%. Under the evaluated conditions, stability tests confirmed that the compounds remained stable, with relative standard deviations below 13.83%. Consequently, the UHPLC-MS\/MS method was effectively used to determine the pharmacokinetics of fourteen components in rat plasma after oral administration of GR extract. This study provides supportive data for rational application of GR.<\/jats:p>","DOI":"10.3390\/molecules30224404","type":"journal-article","created":{"date-parts":[[2025,11,14]],"date-time":"2025-11-14T11:49:43Z","timestamp":1763120983000},"page":"4404","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Simultaneous Quantification of Multiple Analytes in Rat Plasma by UHPLC\u2013MS\/MS Following Oral Administration of Gastrodiae Rhizoma Extract for Pharmacokinetic Evaluation"],"prefix":"10.3390","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-7877-8274","authenticated-orcid":false,"given":"Lu","family":"Chen","sequence":"first","affiliation":[{"name":"State Key Laboratory of Chinese Medicine Modernization, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8735-165X","authenticated-orcid":false,"given":"Yameng","family":"Zhu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Chinese Medicine Modernization, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7742-124X","authenticated-orcid":false,"given":"Huizi","family":"Ouyang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Chinese Medicine Modernization, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiwei","family":"Wu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Chinese Medicine Modernization, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenhan","family":"Lin","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Chinese Medicine Modernization, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-5377-3738","authenticated-orcid":false,"given":"Kaili","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Chinese Medicine Modernization, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3781-9234","authenticated-orcid":false,"given":"Jun","family":"He","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Chinese Medicine Modernization, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/S2225-4110(16)30054-2","article-title":"Gastrodiae Rhizoma (Ti\u0101n M\u00e1): A Review of Biological Activity and Antidepressant Mechanisms","volume":"1","author":"Chen","year":"2011","journal-title":"J. Tradit. Complement. Med."},{"key":"ref_2","unstructured":"Chinese Pharmacopoeia Commission (2025). Pharmacopoeia of the People\u2019s Republic of China, Chinese Pharmacopoeia Commission. [2025 ed.]."},{"key":"ref_3","first-page":"155518","article-title":"Gastrodin Regulates the TLR4\/TRAF6\/NF-\u03baB Pathway to Reduce Neuroinflammation and Microglial Activation in an AD Model","volume":"128","author":"Wang","year":"2024","journal-title":"Phytomed. Int. J. Phytother. Phytopharm."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.jep.2016.03.018","article-title":"The Aqueous Extract of Rhizome of Gastrodia Elata Blume Attenuates Locomotor Defect and Inflammation after Traumatic Brain Injury in Rats","volume":"185","author":"Ng","year":"2016","journal-title":"J. Ethnopharmacol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"112403","DOI":"10.1016\/j.jep.2019.112403","article-title":"Therapeutic Assessment of Fractions of Gastrodiae Rhizoma on Chronic Atrophic Gastritis by 1H NMR-Based Metabolomics","volume":"254","author":"Xu","year":"2020","journal-title":"J. Ethnopharmacol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"115832","DOI":"10.1016\/j.jep.2022.115832","article-title":"Anti-Depressant-like Effect of Fermented Gastrodia Elata Bl. by Regulating Monoamine Levels and BDNF\/NMDAR Pathways in Mice","volume":"301","author":"Gao","year":"2023","journal-title":"J. Ethnopharmacol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1620","DOI":"10.3390\/ijms13021620","article-title":"Acidic Polysaccharide Extracts from Gastrodia Rhizomes Suppress the Atherosclerosis Risk Index through Inhibition of the Serum Cholesterol Composition in Sprague Dawley Rats Fed a High-Fat Diet","volume":"13","author":"Kim","year":"2012","journal-title":"Int. J. Mol. Sci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"698","DOI":"10.3390\/ijms13010698","article-title":"Effects of Acidic Polysaccharides from Gastrodia Rhizome on Systolic Blood Pressure and Serum Lipid Concentrations in Spontaneously Hypertensive Rats Fed a High-Fat Diet","volume":"13","author":"Lee","year":"2012","journal-title":"Int. J. Mol. Sci."},{"key":"ref_9","first-page":"155369","article-title":"Gastrodin Alleviates Mitochondrial Dysfunction by Regulating SIRT3-Mediated TFAM Acetylation in Vascular Dementia","volume":"128","author":"Chen","year":"2024","journal-title":"Phytomed. Int. J. Phytother. Phytopharm."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"113751","DOI":"10.1016\/j.jep.2020.113751","article-title":"Gastrodin Alleviates Seizure Severity and Neuronal Excitotoxicities in the Rat Lithium-Pilocarpine Model of Temporal Lobe Epilepsy via Enhancing GABAergic Transmission","volume":"269","author":"Yang","year":"2021","journal-title":"J. Ethnopharmacol."},{"key":"ref_11","first-page":"153576","article-title":"Gastrodiae Rhizoma Attenuates Brain Aging via Promoting Neuritogenesis and Neurodifferentiation","volume":"87","author":"Hsu","year":"2021","journal-title":"Phytomed. Int. J. Phytother. Phytopharm."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Kim, S., Choi, J.G., Kim, S.W., Park, S.C., Kang, Y.-R., Park, D.S., Son, M., and Lee, C.H. (2022). Inhibition of \u03b1-Synuclein Aggregation by MT101-5 Is Neuroprotective in Mouse Models of Parkinson\u2019s Disease. Biomed. Pharmacother., 154.","DOI":"10.1016\/j.biopha.2022.113637"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"111593","DOI":"10.1016\/j.intimp.2024.111593","article-title":"Gastrodin Ameliorates Acute Pancreatitis by Modulating Macrophage Inflammation Cascade via Inhibition the P38\/NF-\u03baB Pathway","volume":"129","author":"Jiang","year":"2024","journal-title":"Int. Immunopharmacol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Ma, L., Liu, Z., Kim, E., Huang, K., Kim, C.Y., Kim, H., Park, K., Kwon, W.-S., Lee, S.I., and Kim, Y.-G. (2024). Parishin A Inhibits Oral Squamous Cell Carcinoma via the AKT\/mTOR Signaling Pathway. Pharmaceuticals, 17.","DOI":"10.3390\/ph17101277"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Cheng, X., Sun, J., Chen, S., Wang, N., Tang, W., Xia, Z., Shu, Y., Gao, S., Wang, Z., and Wang, X. (2024). Parishin B Blocking TRIB3-AKT1 Interaction Inhibits Breast Cancer Lung Metastasis. Front. Pharmacol., 15.","DOI":"10.3389\/fphar.2024.1517708"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/j.apsb.2016.03.009","article-title":"Parishin C\u2019s Prevention of A\u03b2 1-42-Induced Inhibition of Long-Term Potentiation Is Related to NMDA Receptors","volume":"6","author":"Liu","year":"2016","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"117891","DOI":"10.1016\/j.jep.2024.117891","article-title":"Antidepressant Effects of Parishin C in Chronic Social Defeat Stress-Induced Depressive Mice","volume":"325","author":"Jiang","year":"2024","journal-title":"J. Ethnopharmacol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Lai, M.-C., Liu, W.-Y., Liou, S.-S., and Liu, I.-M. (2022). P-Hydroxybenzyl Alcohol Antagonized the ROS-Dependent JNK\/Jun\/Caspase-3 Pathway to Produce Neuroprotection in a Cellular Model of Parkinson\u2019s Disease. Nutrients, 14.","DOI":"10.3390\/nu14235002"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"108728","DOI":"10.1016\/j.pharmthera.2024.108728","article-title":"A Comprehensive Review on Pharmacokinetic Mechanism of Herb-Herb\/Drug Interactions in Chinese Herbal Formula","volume":"264","author":"Li","year":"2024","journal-title":"Pharmacol. Ther."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.jep.2015.10.007","article-title":"Comparative Pharmacokinetics of Gastrodin in Rats after Intragastric Administration of Free Gastrodin, Parishin and Gastrodia Elata Extract","volume":"176","author":"Tang","year":"2015","journal-title":"J. Ethnopharmacol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/j.aca.2007.03.035","article-title":"Analysis of Brain Distribution and Biliary Excretion of a Nutrient Supplement, Gastrodin, in Rat","volume":"590","author":"Lin","year":"2007","journal-title":"Anal. Chim. Acta"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Liu, J., Chen, S., Cheng, J., Zhang, J., Wang, Y., and Liu, A. (2017). An Optimized and Sensitive Pharmacokinetic Quantitative Method of Investigating Gastrodin, Parishin, and Parishin B, C and E in Beagle Dog Plasma Using LC-MS\/MS after Intragastric Administration of Tall Gastrodia Capsules. Molecules, 22.","DOI":"10.3390\/molecules22111938"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/j.jpba.2014.08.017","article-title":"Relative Bioavailability of Gastrodin and Parishin from Extract and Powder of Gastrodiae Rhizoma in Rat","volume":"100","author":"Zhao","year":"2014","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1913","DOI":"10.1002\/bmc.3516","article-title":"Analysis of the Metabolic Profile of Parishin by Ultra-performance Liquid Chromatography\/Quadrupole-Time of Flight Mass Spectrometry","volume":"29","author":"Tang","year":"2015","journal-title":"Biomed. Chromatogr."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.1007\/s11095-024-03720-3","article-title":"Effects of Three Kinds of Carbohydrate Pharmaceutical Excipients\u2014Fructose, Lactose and Arabic Gum on Intestinal Absorption of Gastrodin through Glucose Transport Pathway in Rats","volume":"41","author":"Chen","year":"2024","journal-title":"Pharm. Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1007\/s13659-019-00224-1","article-title":"Gastrodin Derivatives from Gastrodia Elata","volume":"9","author":"Xu","year":"2019","journal-title":"Nat. Prod. Bioprospect."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1186\/s40543-020-00211-z","article-title":"A Simplified LC\u2212MS\/MS Approach for Simultaneous Quantification and Pharmacokinetics of Five Compounds in Rats Following Oral Administration of Gastrodia Elata Extract","volume":"11","author":"Dong","year":"2020","journal-title":"J. Anal. Sci. Technol."},{"key":"ref_28","first-page":"21","article-title":"Development of a Fully Automated On-Line Solid Phase Extraction and High-Performance Liquid Chromatography with Diode Array Detection Method for the Pharmacokinetic Evaluation of Bavachinin: A Study on Absolute Bioavailability and Dose Proportionality","volume":"893\u2013894","author":"Liu","year":"2012","journal-title":"J. Chromatogr. B"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1002\/cpt.3146","article-title":"Impact of Pregnancy on the Pharmacokinetics and Metabolism of Nicotinamide in Humans","volume":"115","author":"Fashe","year":"2024","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Jiang, Z., Zheng, X., Gong, X., Zhao, C., Zhou, X., Zhao, Y., and Yan, Y. (2017). Relative Tissue Distribution and Excretion Studies of Gastrodin and Parishin from Powder and Extract of Gastrodiae Rhizoma in Rat by UHPLC-ESI-MS\/MS. Biomed. Chromatogr., 31.","DOI":"10.1002\/bmc.3909"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Wu, J., Wu, B., Tang, C., and Zhao, J. (2017). Analytical Techniques and Pharmacokinetics of Gastrodia Elata Blume and Its Constituents. Molecules, 22.","DOI":"10.3390\/molecules22071137"},{"key":"ref_32","first-page":"156229","article-title":"Gastrodin Reduces A\u03b2 Brain Levels in an Alzheimer\u2019s Disease Mouse Model by Inhibiting P-Glycoprotein Ubiquitination","volume":"135","author":"Zhu","year":"2024","journal-title":"Phytomed. Int. J. Phytother. Phytopharm."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Percie du Sert, N., Hurst, V., Ahluwalia, A., Alam, S., Avey, M.T., Baker, M., Browne, W.J., Clark, A., Cuthill, I.C., and Dirnagl, U. (2020). The ARRIVE Guidelines 2.0: Updated Guidelines for Reporting Animal Research. PLoS Biol., 18.","DOI":"10.1371\/journal.pbio.3000410"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Shang, Y., Zhu, Y., Zhang, K., Zhang, Z., Geng, H., Liu, X., Li, W., Chen, L., Li, C., and Liu, Y. (2025). The Pharmacokinetics, Bioavailability, and Excretion Studies of \u03b1-Cyperone in Rats by UHPLC-QQQ-MS\/MS. Molecules, 30.","DOI":"10.3390\/molecules30193899"},{"key":"ref_35","unstructured":"U.S. Food and Drug Administration (2025, March 25). M10 Bioanalytical Method Validation and Study Sample Analysis, Available online: https:\/\/www.fda.gov\/media\/162903\/download."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/30\/22\/4404\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,14]],"date-time":"2025-11-14T11:49:58Z","timestamp":1763120998000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/30\/22\/4404"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,14]]},"references-count":35,"journal-issue":{"issue":"22","published-online":{"date-parts":[[2025,11]]}},"alternative-id":["molecules30224404"],"URL":"https:\/\/doi.org\/10.3390\/molecules30224404","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,14]]}}}