title: LC-MS/MS Determination and Pharmacokinetic Study of Pedunculoside in Rat Plasma after Oral Administration of Pedunculoside and Ilex rotunda Extract.
abstract: Ilex rotunda is widely used to treat many disorders as a traditional Chinese medicine (TCM) containing 4%-5% pedunculoside (PDC). A rapid, selective, and sensitive liquid chromatography-tandem mass spectrometry method (LC-MS/MS) was developed and validated to determine PDC in rat plasma by using 3β,19α-dihydroxyurs-12-en-28-oic acid 28-β-D-glucopyranosyl ester (DEOG) as an internal standard. The analytes were extracted by protein precipitation and eluted on a C18 chromatography column using a mobile phase of methanol-H2O (70:30, v/v) delivered at a flow rate of 0.6 mL/min. Detection was performed using positive ion electrospray ionization in multiple reaction monitoring modes. The assay was linear over the concentration range of 0.60 ng/mL to 200 ng/mL, with a quantification limit of 0.60 ng/mL. Intra-day and inter-day precisions (%RSD) ranged from 2.12 to 9.51 for PDC, whereas the accuracy was within -7.83%~9.40%. The validated method was successfully applied to the pharmacokinetic study of PDC in rat plasma after oral administration of pure PDC and Ilex rotunda extract (IRE). Pharmacokinetic parameters of PDC in IRE, such as Cmax, AUC0-t, AUC0-∞, t1/2z, and CLz/F, statistically differed from those of the pure monomer (p < 0.01). However, Tmax and MRT showed no significant differences between the two groups. Results suggested that other coexisting components in IRE may decrease the absorption of PDC. Compound-compound interactions between PDC and other herbal extract components can alter the pharmacokinetic behavior of PDC. The study will be helpful in providing references for understanding the action mechanism and clinical application of Ilex rotunda.
authors.affiliation: Cardiovascular Medicine, the First Hospital of Jilin University, Changchun 130021, China. zhao241241241@sina.cn.
authors.forename: Waiou
authors.initials: W
authors.lastname: Zhao
authors.affiliation: Emergency Department, the First Hospital of Jilin University, Changchun 130021, China. qw_ywyq4479@126.com.
authors.forename: Li
authors.initials: L
authors.lastname: Pang
authors.affiliation: Emergency Department, the First Hospital of Jilin University, Changchun 130021, China. sah211@sina.cn.
authors.forename: Dahai
authors.initials: D
authors.lastname: Xu
authors.affiliation: Emergency Department, the First Hospital of Jilin University, Changchun 130021, China. zhangreru@163.com.
authors.forename: Nan
authors.initials: N
authors.lastname: Zhang
mesh_terms: D000284:Administration, Oral; D000818:Animals; D002853:Chromatography, Liquid / Q000379:methods; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000493:pharmacokinetics; D005947:Glucose / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D030017:Ilex / Q000737:chemistry*; D008297:Male; D013058:Mass Spectrometry / Q000379:methods; D010936:Plant Extracts / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D014315:Triterpenes / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: D004365:Drugs, Chinese Herbal; D010936:Plant Extracts; D014315:Triterpenes; C084241:pedunculoside; D005947:Glucose
keywords: Ilex rotunda; LC-MS/MS; pedunculoside; pharmacokinetics