Multi-Component Comparative Pharmacokinetics in Rats After Oral Administration of Fructus aurantii Extract, Naringin, Neohesperidin, and Naringin-Neohesperidin

Abstract

Citrus × aurantium L., Chinese name: Fructus Aurantii (FA) has been largely used as Qiinvigorating herb in China for centuries. The main components (meranzin hydrate, naringin, neohesperidin, meranzin, nobiletin) have good physiological activity with relatively high abundance in FA. Few multi-component comparative pharmacokinetics are simultaneously accessible for the flavone glycosides, polymethoxy flavones, and coumarins in FA. In this work, a reliable and rapid ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was established and validated to determine the five ingredients in the SD rat plasma, and further applied to the pharmacokinetic studies after oral administration of monomer, drugs in compatibility, and FA extract. After hydrolysis with b-glucuronidase and sulfatase, the concentration of naringin and neohesperidin in rat plasma were expressed respectively by the total concentration of naringenin and hesperitin which was determined by UPLC-MS/MS. Double-peak phenomenon was observed for naringin and neohesperidin, which may be due to the enterohepatic circulation or multiple site absorption of the two flavone glycosides. Meranzin hydrate and meranzin (coumarins) were absorbed rapidly (T max, about 1.0 h) but eliminated slowly (t 1/2z exceeds 6.5 h). Nobiletin, a typical polymethoxy flavone, was also rapidly absorbed according to T max and AUC (0-t) . DAS 3.1 software suggests the pharmacokinetic profiles of the five components in rats be depicted as a two-compartment pharmacokinetic model. There were significant differences in pharmacokinetic parameters for naringenin and hesperetin between the compatibility, FA extract group vs monomer group: ① remarkable increases in the values of AUC (0-∞) , AUC (0-t) and C max ; ② obvious decrease of CL Z/F ; and ③ longer t max and t 1/2z . The results suggest that compatibility can promote mutual absorption and affect the elimination behaviors.

Metabolic regularity of bioactive compounds in Bufei Jianpi granule in rats using ultra‐high‐performance liquid chromatography coupled with triple quadrupole mass spectrometry analysis technology

“…The half‐lives of peimine, peiminine, astragaloside IV, nobiletin, naringin, and formononetin in BJG compound administration were significantly longer than those in monomer administration (Chen et al, 2013; Du et al, 2005; Luo et al, 2018; Yuan et al, 2020). Compared with monomer administration, the T max of some ingredients was similar to that of BJG compound administration (e.g., peimine, formononetin, and magnolol), with some significantly longer (e.g., nobiletin) and some significantly shorter (e.g., peiminine and naringin).…”

Comparative pharmacokinetics of the main active components in normal and ulcerative colitis rats after oral administration of Zingiberis Rhizoma–Ginseng Radix et Rhizoma herb pair and its single herb extracts by LC–MS/MS

“…Notably, as displayed in Figure 2, the bimodal phenomenon of average blood concentration curves for ginsenoside Re, ginsenoside Rg1, ginsenoside Rb1, and 6‐gingerol was exhibited, which might be related to the enterohepatic circulation and separated “absorption windows” [29]. Additionally, the reciprocal transformation between 6‐gingerol and glucuronide metabolites was a possible cause of the double‐peak phenomenon [30], and the other reason might be the inversion of other similar compounds in ginsenosides (such as ginsenoside Rd could be converted to ginsenoside Rb1 by intestinal microbes), which led to double absorption [31].…”

Comparative Studies on Multi-Component Pharmacokinetics of Polygonum multiflorum Thunb Extract After Oral Administration in Different Rat Models

“…The UPLC-MS/MS method for determining the nine ingredients in rat blood plasma was validated according to the current US FDA Bioanalytical Method Validation Guidance (Guidance for Industry: Bioanalytical Method Validation, 2001) (Yuan et al, 2020). The following parameters were determined: specificity, linearity, lower limit of quantitation (LLOQ), accuracy, precision, extraction recovery, matrix effect, and stability.…”