{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,30]],"date-time":"2025-08-30T16:41:48Z","timestamp":1756572108553,"version":"3.41.2"},"reference-count":19,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,1,20]],"date-time":"2022-01-20T00:00:00Z","timestamp":1642636800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>Umbralisib is a dual inhibitor of phosphatidylinositol 3-kinase delta (PI3K\u03b4) and casein kinase 1 epsilon (CK1\u03b5) for treating marginal zone lymphoma (MZL) and follicular lymphoma (FL). This study aimed to develop a fast and stable ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS\/MS) method for quantitative analysis of umbralisib in rat plasma and its application for evaluating the effect of sophocarpine on the pharmacokinetics of umbralisib. A direct protein preparation with acetonitrile was used to deal with rat plasma. Umbralisib and duvelisib (internal standard, IS) were isolated on a Waters Acquity UPLC BEH C18 column with mobile phase consisted of acetonitrile and 0.1% formic acid in water. The linear range was from 0.5 to 1,000\u00a0ng\/ml. Both of the precision (RSD%) and accuracy (RE%) were less than 15% in a permissible range. The mean recovery and matrix effect of umbralisib were 86.3\u201396.2% and 97.8\u2013112.0%, respectively. When umbralisib was combined with sophocarpine, AUC<jats:sub>0\u2192\u221e<\/jats:sub> of umbralisib was significantly reduced to 2462.799 \u00b1 535.736\u00a0ng\/ml\u2022h from 5416.665 \u00b1 1,451.846\u00a0ng\/ml\u2022h, and C<jats:sub>max<\/jats:sub> also was markedly diminished. Moreover, CLz\/F was increased more than two times. This developed, optimized and technical UPLC-MS\/MS method was extremely suitable for detecting the concentrations of umbralisib in rat plasma after an oral administration, and sophocarpine significantly changed the pharmacokinetics of umbralisib in rats. This obvious pharmacokinetic changes indicates that there seems to exist herb-drug interaction between sophocarpine and umbralisib.<\/jats:p>","DOI":"10.3389\/fphar.2022.749095","type":"journal-article","created":{"date-parts":[[2022,1,20]],"date-time":"2022-01-20T06:23:06Z","timestamp":1642659786000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Effect of Sophocarpine on the Pharmacokinetics of Umbralisib in Rat Plasma Using a Novel UPLC-MS\/MS Method"],"prefix":"10.3389","volume":"13","author":[{"given":"Qinghua","family":"Weng","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xia","family":"Lan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yingjie","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chen","family":"Fan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ren-ai","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pengzhao","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,1,20]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"486","DOI":"10.1016\/s1470-2045(18)30082-2","article-title":"Umbralisib, a Novel PI3K\u03b4 and Casein Kinase-1\u03b5 Inhibitor, in Relapsed or Refractory Chronic Lymphocytic Leukaemia and Lymphoma: an Open-Label, Phase 1, Dose-Escalation, First-In-Human Study","volume":"19","author":"Burris","year":"2018","journal-title":"Lancet Oncol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"368","DOI":"10.1080\/10428194.2020.1832660","article-title":"Phase 2 Study of Parsaclisib (INCB050465), a Highly Selective, Next-Generation PI3K\u03b4 Inhibitor, in Relapsed or Refractory Diffuse Large B-Cell Lymphoma (CITADEL-202)","volume":"62","author":"Coleman","year":"2021","journal-title":"Leuk. Lymphoma"},{"key":"B3","doi-asserted-by":"publisher","first-page":"857","DOI":"10.1007\/s40265-021-01504-2","article-title":"Umbralisib: First Approval","volume":"81","author":"Dhillon","year":"2021","journal-title":"Drugs"},{"key":"B4","doi-asserted-by":"publisher","first-page":"714","DOI":"10.1016\/j.neo.2020.10.004","article-title":"SHC014748M, a Novel Selective Inhi-Bitor of PI3K\u03b4, Demonstrates Promising Preclinical Antitumor Activity in B Cell Lymphomas and Chronic Lymphocytic Leukemia","volume":"22","author":"Fan","year":"2020","journal-title":"Neoplasia"},{"unstructured":"FDA Approved Drug Products: UKONIQ (Umbralisib) Tablets, for Oral Use. [Online]2021","key":"B5"},{"key":"B6","doi-asserted-by":"publisher","first-page":"1609","DOI":"10.1200\/JCO.20.03433","article-title":"Umbralisib, a Dual PI3K\u03b4\/CK1\u03b5 Inhibitor in Patients with Relapsed or Refractory Indolent Lymphoma","volume":"39","author":"Fowler","year":"2021","journal-title":"J. Clin. Oncol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"616","DOI":"10.2741\/4740","article-title":"Sophocarpine Inhibits the Growth of Gastric Cancer Cells via Autophagy and Apoptosis","volume":"24","author":"Huang","year":"2019","journal-title":"Front. Biosci. (Landmark Ed."},{"key":"B8","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1007\/s00277-018-3501-8","article-title":"Burden of Illness of Follicular Lymphoma and Marginal Zone Lymphoma","volume":"98","author":"Monga","year":"2019","journal-title":"Ann. Hematol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. Clin."},{"key":"B10","doi-asserted-by":"publisher","first-page":"626897","DOI":"10.3389\/fphar.2020.626897","article-title":"In Vivo Pharmacokinetic Drug-Drug Interaction Studies between Fedratinib and Antifungal Agents Based on a Newly Developed and Validated UPLC\/MS-MS Method","volume":"11","author":"Tang","year":"2020","journal-title":"Front. Pharmacol."},{"unstructured":"TG Therapeutics. UKONIQTM (Umbralisib): US Prescribing Information2021","key":"B11"},{"key":"B12","doi-asserted-by":"publisher","first-page":"1830","DOI":"10.1248\/bpb.b19-00353","article-title":"Sophocarpine Inhibits Tumorgenesis of Colorectal Cancer via Downregulation of MEK\/ERK\/VEGF Pathway","volume":"42","author":"Wang","year":"2019","journal-title":"Biol. Pharm. Bull."},{"key":"B13","doi-asserted-by":"publisher","first-page":"418","DOI":"10.1002\/jssc.201900824","article-title":"An Ultra High Performance Liquid Chromatography with Tandem Mass Spectrometry Method for Simultaneous Determination of Thirteen Components Extracted from Radix Puerariae in Rat Plasma and Tissues: Application to Pharmacokinetic and Tissue Distribution Study","volume":"43","author":"Wei","year":"2020","journal-title":"J. Sep. Sci."},{"key":"B14","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1016\/j.jpba.2018.12.036","article-title":"UPLC-MS\/MS Method for the Simultaneous Determination of Imatinib, Voriconazole and Their Metabolites Concentrations in Rat Plasma","volume":"166","author":"Xu","year":"2019","journal-title":"J. Pharm. Biomed. Anal."},{"key":"B15","doi-asserted-by":"publisher","first-page":"1263","DOI":"10.1007\/s00210-020-02032-8","article-title":"Sophocarpine Can Enhance the Inhibiting Effect of Oxaliplatin on colon Cancer Liver Metastasis-In Vitro and In Vivo","volume":"394","author":"Yang","year":"2021","journal-title":"Naunyn Schmiedebergs Arch. Pharmacol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"1127","DOI":"10.1080\/00498254.2018.1468047","article-title":"In Vitro inhibitory Effects of Sophocarpine on Human Liver Cytochrome P450 Enzymes","volume":"49","author":"Zhang","year":"2019","journal-title":"Xenobiotica"},{"key":"B17","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1016\/j.canlet.2016.01.011","article-title":"Differentiation Therapy of Hepatocellular Carcinoma by Inhibiting the Activity of AKT\/GSK-3\u03b2\/\u03b2-catenin axis and TGF-\u03b2 Induced EMT with Sophocarpine","volume":"376","author":"Zhang","year":"2016","journal-title":"Cancer Lett."},{"key":"B18","doi-asserted-by":"publisher","first-page":"3590","DOI":"10.1002\/jssc.201701504","article-title":"Salt-assisted Dispersive Liquid-Liquid Microextraction for Enhancing the Concentration of Matrine Alkaloids in Traditional Chinese Medicine and its Preparations","volume":"41","author":"Zhang","year":"2018","journal-title":"J. Sep. Sci."},{"key":"B19","doi-asserted-by":"publisher","first-page":"406","DOI":"10.1002\/jssc.201900670","article-title":"Simultaneous Determination of Eight Bioactive Constituents of Zhi-Zi-Hou-Po Decoction in Rat Plasma by Ultra High Performance Liquid Chromatography with Tandem Mass Spectrometry and its Application to a Pharmacokinetic Study","volume":"43","author":"Zhu","year":"2020","journal-title":"J. Sep. Sci."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2022.749095\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,1,20]],"date-time":"2022-01-20T06:23:08Z","timestamp":1642659788000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2022.749095\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,20]]},"references-count":19,"alternative-id":["10.3389\/fphar.2022.749095"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2022.749095","relation":{},"ISSN":["1663-9812"],"issn-type":[{"type":"electronic","value":"1663-9812"}],"subject":[],"published":{"date-parts":[[2022,1,20]]},"article-number":"749095"}}