{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,13]],"date-time":"2026-09-13T10:00:36Z","timestamp":1789293636409,"version":"build-2803163510"},"reference-count":55,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2023,6,8]],"date-time":"2023-06-08T00:00:00Z","timestamp":1686182400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Council of Scientific and Industrial Research"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Cissus quadrangularis is a nutrient-rich plant with a history of use in traditional medicine. It boasts a diverse range of polyphenols, including quercetin, resveratrol, \u03b2-sitosterol, myricetin, and other compounds. We developed and validated a sensitive LC-MS\/MS method to quantify quercetin and t-res biomarkers in rat serum and applied this method to pharmacokinetic and stability studies. The mass spectrometer was set to negative ionization mode for the quantification of quercetin and t-res. Phenomenex Luna (C18(2), 100 A, 75 \u00d7 4.6 mm, 3 \u00b5) column was utilized to separate the analytes using an isocratic mobile phase consisting of methanol and 0.1% formic acid in water (82:18). Validation of the method was performed using various parameters, including linearity, specificity, accuracy, stability, intra-day, inter-day precision, and the matrix effect. There was no observed significant endogenous interference from the blank serum. The analysis was completed within 5.0 min for each run, and the lower limit of quantification was 5 ng\/mL. The calibration curves showed a linear range with a high correlation coefficient (r2 &gt; 0.99). The precision for intra- and inter-day assays showed relative standard deviations from 3.32% to 8.86% and 4.35% to 9.61%, respectively. The analytes in rat serum were stable during bench-top, freeze-thaw, and autosampler (\u22124 \u00b0C) stability studies. After oral administration, the analytes showed rapid absorption but underwent metabolism in rat liver microsomes despite being stable in simulated gastric and intestinal fluids. Intragastric administration resulted in higher absorption of quercetin and t-res, with greater Cmax, shorter half-life, and improved elimination. No prior research has been conducted on the oral pharmacokinetics and stability of anti-diabetic compounds in the Ethanolic extract of Cissus quadrangularis EECQ, making this the first report. Our findings can provide the knowledge of EECQ\u2019s bioanalysis and pharmacokinetic properties which is useful for future clinical trials.<\/jats:p>","DOI":"10.3390\/molecules28124656","type":"journal-article","created":{"date-parts":[[2023,6,9]],"date-time":"2023-06-09T02:03:18Z","timestamp":1686276198000},"page":"4656","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Simultaneous Estimation of Quercetin and trans-Resveratrol in Cissus quadrangularis Extract in Rat Serum Using Validated LC-MS\/MS Method: Application to Pharmacokinetic and Stability Studies"],"prefix":"10.3390","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7261-320X","authenticated-orcid":false,"given":"Shailesh D.","family":"Dadge","sequence":"first","affiliation":[{"name":"Pharmaceutics & Pharmacokinetics Division, CSIR-Central Drug Research Institute (CSIR-CDRI), Sitapur Road, Lucknow 226031, India"},{"name":"Academy of Scientific and Innovative Research, Ghaziabad 201002, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anees A.","family":"Syed","sequence":"additional","affiliation":[{"name":"Pharmaceutics & Pharmacokinetics Division, CSIR-Central Drug Research Institute (CSIR-CDRI), Sitapur Road, Lucknow 226031, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1086-2339","authenticated-orcid":false,"given":"Athar","family":"Husain","sequence":"additional","affiliation":[{"name":"Pharmaceutics & Pharmacokinetics Division, CSIR-Central Drug Research Institute (CSIR-CDRI), Sitapur Road, Lucknow 226031, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1180-2530","authenticated-orcid":false,"given":"Guru R.","family":"Valicherla","sequence":"additional","affiliation":[{"name":"Pharmaceutics & Pharmacokinetics Division, CSIR-Central Drug Research Institute (CSIR-CDRI), Sitapur Road, Lucknow 226031, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7703-9307","authenticated-orcid":false,"given":"Jiaur R.","family":"Gayen","sequence":"additional","affiliation":[{"name":"Pharmaceutics & Pharmacokinetics Division, CSIR-Central Drug Research Institute (CSIR-CDRI), Sitapur Road, Lucknow 226031, India"},{"name":"Academy of Scientific and Innovative Research, Ghaziabad 201002, India"},{"name":"Pharmacology Division, CSIR-Central Drug Research Institute (CSIR-CDRI), Lucknow 226031, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"153373","DOI":"10.1016\/j.tox.2022.153373","article-title":"Evaluation of mutagenic, cytotoxic, mitochondrial dysfunction, apoptotic activity, and acute toxicity of ethanolic extract of Cissus quadrangularis","volume":"483","author":"Syed","year":"2023","journal-title":"Toxicology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1097\/MCO.0b013e32831394b8","article-title":"Quercetin: Potentials in the prevention and therapy of disease","volume":"11","author":"Bischoff","year":"2008","journal-title":"Curr. Opin. Clin. Nutr. Metab. Care"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1851","DOI":"10.2337\/diabetes.51.6.1851","article-title":"Antidiabetic effects of Panax ginseng berry extract and the identification of an effective component","volume":"51","author":"Attele","year":"2002","journal-title":"Diabetes"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/j.jep.2004.05.012","article-title":"Assessing African medicinal plants for efficacy and safety: Pharmacological screening and toxicology","volume":"94","author":"Fennell","year":"2004","journal-title":"J. Ethnopharmacol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"118118","DOI":"10.1016\/j.lfs.2020.118118","article-title":"Naringin ameliorates type 2 diabetes mellitus-induced steatohepatitis by inhibiting RAGE\/NF-\u03baB mediated mitochondrial apoptosis","volume":"257","author":"Syed","year":"2020","journal-title":"Life Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1016\/j.jep.2016.10.008","article-title":"Evaluation of anti-hypertensive activity of Ulmus wallichiana extract and fraction in SHR, DOCA-salt-and L-NAME-induced hypertensive rats","volume":"193","author":"Syed","year":"2016","journal-title":"J. Ethnopharmacol."},{"key":"ref_7","first-page":"127","article-title":"Heavy metal and phytochemical screening of anti-jaundice and anti-malaria concoctions and genotoxicity assessment of the concoctions using Allium cepa assay","volume":"2","author":"Arojojoye","year":"2015","journal-title":"Trop. Plant Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2014\/215084","article-title":"Evaluation of antioxidant and DNA damage protection activity of the hydroalcoholic extract of Desmostachya bipinnata L. Stapf","volume":"2014","author":"Golla","year":"2014","journal-title":"Sci. World J."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"25","DOI":"10.4103\/0975-9476.128852","article-title":"Protective effect of Cissus quadrangularis Linn. on diabetes induced delayed fetal skeletal ossification","volume":"5","author":"Sirasanagandla","year":"2014","journal-title":"J. Ayurveda Integr. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1442","DOI":"10.1093\/jpp\/rgab078","article-title":"Cissus quadrangularis extract attenuates diabetic nephropathy by altering SIRT1\/DNMT1 axis","volume":"73","author":"Syed","year":"2021","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1080\/1354750X.2022.2107703","article-title":"Cissus quadrangularis extract mitigates diabetic cardiomyopathy by inhibiting RAAS activation, inflammation and oxidative stress","volume":"27","author":"Syed","year":"2022","journal-title":"Biomarkers"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"111681","DOI":"10.1016\/j.exger.2021.111681","article-title":"Polyphenolic-rich Cissus quadrangularis extract ameliorates insulin resistance by activating AdipoR1 in peri-\/post-menopausal rats","volume":"159","author":"Syed","year":"2022","journal-title":"Exp. Gerontol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1080\/10641963.2021.1991942","article-title":"Ethanolic extract of Cissus quadrangularis improves vasoreactivity by modulation of eNOS expression and oxidative stress in spontaneously hypertensive rats","volume":"44","author":"Syed","year":"2022","journal-title":"Clin. Exp. Hypertens."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"962","DOI":"10.31018\/jans.v13i3.2835","article-title":"In vitro anti-inflammatory, anti-diabetic and antioxidant potential of Cissus quadrangularis along with its orexigenic activity in Drosophila melanogaster","volume":"13","author":"Zaki","year":"2021","journal-title":"J. Appl. Nat. Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1515\/jbcpp-2014-0035","article-title":"Involvement of opioidergic and serotonergic systems in the analgesic activity of Cissus quadrangularis L. stem extract in mice","volume":"26","author":"Nie","year":"2015","journal-title":"J. Basic Clin. Physiol. Pharmacol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1002\/ptr.4846","article-title":"A review and evaluation of the efficacy and safety of Cissus quadrangularis extracts","volume":"27","author":"Stohs","year":"2013","journal-title":"Phytother. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"5742981","DOI":"10.1155\/2021\/5742981","article-title":"Anti-inflammatory and antimicrobial potential of Cissus quadrangularis-assisted copper oxide nanoparticles","volume":"2021","author":"Rajeshkumar","year":"2021","journal-title":"J. Nanomater."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1302","DOI":"10.1016\/j.sjbs.2020.01.005","article-title":"Phytochemical characteristics of aerial part of Cissus quadrangularis (L) and its in-vitro inhibitory activity against lukemic cells and antioxidant properties","volume":"27","author":"Dhanasekaran","year":"2020","journal-title":"Saudi J. Biol. Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1694","DOI":"10.1021\/np9902744","article-title":"Stilbene derivatives from Cissus quadrangularis","volume":"62","author":"Adesanya","year":"1999","journal-title":"J. Nat. Prod."},{"key":"ref_20","first-page":"25","article-title":"Chemical constituents and melanin promotion activity of Cissus quadrangularis Linn","volume":"1","author":"Rao","year":"2011","journal-title":"Res. J. Chem. Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1002\/ptr.5783","article-title":"Efficacy and safety of Cissus quadrangularis L. in clinical use: A systematic review and meta-analysis of randomized controlled trials","volume":"31","author":"Sawangjit","year":"2017","journal-title":"Phytother. Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"114355","DOI":"10.1016\/j.jep.2021.114355","article-title":"Cissus quadrangularis L: A comprehensive multidisciplinary review","volume":"279","author":"Bafna","year":"2021","journal-title":"J. Ethnopharmacol."},{"key":"ref_23","first-page":"75","article-title":"Prodrugs of Quercetin and Resveratrol: A Strategy Under development","volume":"19","author":"Biasutto","year":"2014","journal-title":"Curr. Drug Metabolism."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e47","DOI":"10.1017\/jns.2016.41","article-title":"Flavonoids: An overview","volume":"5","author":"Panche","year":"2016","journal-title":"J. Nutr. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/j.canlet.2008.03.046","article-title":"Multitargeted cancer prevention by quercetin","volume":"269","author":"Murakami","year":"2008","journal-title":"Cancer Lett."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"6721","DOI":"10.1016\/j.bmcl.2009.09.114","article-title":"Soluble polyphenols: Synthesis and bioavailability of 3, 4\u2032, 5-tri (\u03b1-d-glucose-3-O-succinyl) resveratrol","volume":"19","author":"Biasutto","year":"2009","journal-title":"Bioorganic Med. Chem. Lett."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1021\/jm060912x","article-title":"Ester-based precursors to increase the bioavailability of quercetin","volume":"50","author":"Biasutto","year":"2007","journal-title":"J. Med. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"141","DOI":"10.4314\/tjpr.v14i1.20","article-title":"Development and validation of reverse phase high performance chromatography method for determination of olanzapine in microsample rat plasma: Application to preclinical pharmacokinetic study","volume":"14","author":"Pervaiz","year":"2015","journal-title":"Trop. J. Pharm. Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2593","DOI":"10.1007\/s11095-008-9677-1","article-title":"The impact of aqueous solubility and dose on the pharmacokinetic profiles of resveratrol","volume":"25","author":"Das","year":"2008","journal-title":"Pharm. Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/S0378-4347(01)00142-6","article-title":"Ultrasensitive assay for three polyphenols (catechin, quercetin and resveratrol) and their conjugates in biological fluids utilizing gas chromatography with mass selective detection","volume":"757","author":"Soleas","year":"2001","journal-title":"J. Chromatogr. B Biomed. Sci. Appl."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1016\/j.jconrel.2008.10.002","article-title":"Enhancement of gastrointestinal absorption of quercetin by solid lipid nanoparticles","volume":"133","author":"Li","year":"2009","journal-title":"J. Control. Release"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.jchromb.2006.12.043","article-title":"SPE-HPLC method for the determination of four flavonols in rat plasma and urine after oral administration of Abelmoschus manihot extract","volume":"852","author":"Lai","year":"2007","journal-title":"J. Chromatogr. B"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1021\/ac9808831","article-title":"Determination of trans-resveratrol in plasma by HPLC","volume":"71","author":"Juan","year":"1999","journal-title":"Anal. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.jchromb.2005.12.021","article-title":"High-performance liquid chromatography spectrometric analysis of trans-resveratrol in rat plasma","volume":"832","author":"He","year":"2006","journal-title":"J. Chromatogr. B"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1246","DOI":"10.1158\/1055-9965.EPI-07-0022","article-title":"Phase I dose escalation pharmacokinetic study in healthy volunteers of resveratrol, a potential cancer chemopreventive agent","volume":"16","author":"Boocock","year":"2007","journal-title":"Cancer Epidemiol. Biomark. Prev."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1002\/(SICI)1099-0801(199807\/08)12:4<232::AID-BMC740>3.0.CO;2-1","article-title":"Determination of quercetin in human plasma by HPLC with spectrophotometric or electrochemical detection","volume":"12","author":"Jones","year":"1998","journal-title":"Biomed. Chromatogr."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/S1570-0232(03)00398-2","article-title":"High-performance liquid chromatographic determination of quercetin in human plasma and urine utilizing solid-phase extraction and ultraviolet detection","volume":"794","author":"Ishii","year":"2003","journal-title":"J. Chromatogr. B"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1002\/mnfr.200500002","article-title":"Bioavailability of trans-resveratrol from red wine in humans","volume":"49","author":"Vitaglione","year":"2005","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1002\/bdd.605","article-title":"Quercetin pharmacokinetics in humans","volume":"29","author":"Moon","year":"2008","journal-title":"Biopharm. Drug Dispos."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"107","DOI":"10.2174\/1389200003339117","article-title":"Drug-metabolizing enzymes mechanisms and functions","volume":"1","author":"Sheweita","year":"2000","journal-title":"Curr. Drug Metab."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Coe, K.J., and Koudriakova, T.R. (2014). Metabolic stability assessed by liver microsomes and hepatocytes. Optim. Drug Discov. Vitr. Methods, 87\u201399.","DOI":"10.1007\/978-1-62703-742-6_6"},{"key":"ref_42","first-page":"42","article-title":"Interaction of flavonoids with red blood cell membrane lipids and proteins: Antioxidant and antihemolytic effects","volume":"41","author":"Chaudhuri","year":"2007","journal-title":"Food Res. Int."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/S0378-4347(97)00383-6","article-title":"Gas chromatographic analysis of resveratrol in plasma, lipoproteins and cells after in vitro incubations","volume":"702","author":"Blache","year":"1997","journal-title":"J. Chromatogr. B Biomed. Sci. Appl."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1590\/S0102-695X2013000500009","article-title":"Pharmacokinetic study of rutin and quercetin in rats after oral administration of total flavones of mulberry leaf extract","volume":"23","author":"Cao","year":"2013","journal-title":"Rev. Bras. Farm."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1016\/j.bjp.2018.08.011","article-title":"Simultaneous liquid chromatography-tandem mass spectrometry method to quantify epicatechin and procyanidin B2 in rat plasma after oral administration of Trichilia catigua (catuaba) extract and its application to a pharmacokinetic study","volume":"29","author":"Chavari","year":"2019","journal-title":"Rev. Bras. Farmacogn."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"S7","DOI":"10.1002\/mnfr.200800177","article-title":"Pharmacokinetic and safety profile of trans-resveratrol in a rising multiple-dose study in healthy volunteers","volume":"53","author":"Almeida","year":"2009","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/S0009-9120(02)00397-1","article-title":"Absorption of three wine-related polyphenols in three different matrices by healthy subjects","volume":"36","author":"Goldberg","year":"2003","journal-title":"Clin. Biochem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1377","DOI":"10.1124\/dmd.104.000885","article-title":"High absorption but very low bioavailability of oral resveratrol in humans","volume":"32","author":"Walle","year":"2004","journal-title":"Drug Metab. Dispos."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"100021","DOI":"10.1016\/j.phyplu.2021.100021","article-title":"Inhibition of NOX4 by Cissus quadrangularis extract protects from Type 2 diabetes induced-steatohepatitis","volume":"1","author":"Syed","year":"2021","journal-title":"Phytomed. Plus"},{"key":"ref_50","unstructured":"FDA (2001). Bioanalytical Method Validation Guidance for Industry, FDA."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"860","DOI":"10.2174\/138920008786485218","article-title":"Solution stability-plasma, gastrointestinal, bioassay","volume":"9","author":"Di","year":"2008","journal-title":"Curr. Drug Metab."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.jchromb.2018.01.035","article-title":"LC-MS\/MS method for the simultaneous quantification of luteolin, wedelolactone and apigenin in mice plasma using hansen solubility parameters for liquid-liquid extraction: Application to pharmacokinetics of Eclipta alba chloroform fraction","volume":"1081","author":"Cheruvu","year":"2018","journal-title":"J. Chromatogr. B"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/j.jpba.2018.09.031","article-title":"Elucidation of pharmacokinetics of novel DNA ligase I inhibitor, S012-1332 in rats: Integration of in vitro and in vivo findings","volume":"162","author":"Riyazuddin","year":"2019","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1016\/j.jpba.2018.06.047","article-title":"In-vitro metabolism, CYP profiling and metabolite identification of E- and Z- guggulsterone, a potent hypolipidmic agent","volume":"160","author":"Chhonker","year":"2018","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"970","DOI":"10.1124\/dmd.111.044446","article-title":"Metabolism, Pharmacokinetics, Tissue Distribution, and Stability Studies of the Prodrug Analog of an Anti-Hepatitis B Virus Dinucleoside Phosphorothioate","volume":"40","author":"Coughlin","year":"2012","journal-title":"Drug Metab. Dispos."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/28\/12\/4656\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:51:16Z","timestamp":1760125876000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/28\/12\/4656"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6,8]]},"references-count":55,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2023,6]]}},"alternative-id":["molecules28124656"],"URL":"https:\/\/doi.org\/10.3390\/molecules28124656","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,6,8]]}}}