Comparative pharmacokinetics of prim‐O‐glucosylcimifugin and cimifugin by liquid chromatography–mass spectrometry after oral administration of Radix Saposhnikoviae extract, cimifugin monomer solution and prim‐O‐glucosylcimifugin monomer solution to rats

Abstract

A sensitive and reliable liquid chromatography-mass spectrometry method has been developed and validated for simultaneous determination of cimifugin and prim-O-glucosylcimifugin in rat plasma after oral administration of Radix Saposhnikoviae (RS) extract, prim-O-glucosylcimifugin monomer solution and cimifugin monomer solution. Plasma samples were pretreated by protein precipitation with acetonitrile containing the internal standards puerarin and daidzein. LC separation was achieved on a Zorbax SB-C(18) column (150 × 4.6 mm i.d., 5 µm) with 0.1% formic acid in water and methanol by isocratic elution. The detection was carried out in select-ion-monitoring mode with a positive electrospray ionization interface. The fully validated method was successfully applied to the pharmacokinetic study of the analytes in rats. A bimodal phenomenon appeared in the concentration-time curve of prim-O-glucosylcimifugin and cimifugin after oral administration of RS extract. Prim-O-glucosylcimifugin mainly transformed to cimifugin when it was absorbed into blood. Both absorption and elimination of cimifugin after oral administration of RS were longer than after administration of single cimifugin. The pharmacokinetic parameters (AUC(0-t) , AUC(0-∞) and t(1/2) ) of prim-O-glucosylcimifugin and cimifugin by giving cimifugin monomer solution, prim-O-glucosylcimifugin monomer solution and RS extract had significant differences (P < 0.05).

Polysaccharide enhances Radix Saposhnikoviae efficacy through inhibiting chromones decomposition in intestinal tract

“…schischk in family Umbelliferae, and is commonly used for treating febrility, rheumatism, headache, vertigo, generalized aching, convulsion, arthralgia and inflammatory symptoms for thousands of years in China, Japan, and Korea12345. Modern scientific experiments have also confirmed the beneficial effects of RS using its extracts1567.…”

“…RS contains various bioactive substances, such as chromones, coumarins, polyacetylenes, and polysaccharides. Among them, chromones and coumarins are the main components of RS489. Furthermore, chromones have also been identified as the main bioactive constituents with most-evident pharmacological activities as they possess potent analgesic, antifebric, anti-inflammatory and immune-regulatory effects15.…”

“…1). In Chinese pharmacopoeia, PGCN and GML are designated as marker compounds for RS quality control due to their relatively high content and GML is also used for the identification of RS in Japanese Pharmacopoeia341011. Cimifugin is aglycone of PGCN and has much lower content than that of PGCN and GML.…”

“…Cimifugin is aglycone of PGCN and has much lower content than that of PGCN and GML. Huge amount of cimifugin and trace amount of PGCN and GML were detected in the plasma sample of overdose chromone412. Generally, cimifugin is regarded as the pharmacologically active form of inactive chromone derivatives such as PGCN and GML, which are transformed into bioavailable cimifugin in the gastrointestinal tract471112.…”

“…In addition to chromones, several other types of components were also identified in RS, including polysaccharides, coumarins, volatile oils, polyacetylenes, organic acids and so on489. Among these constituents, polysaccharides represent as immune-regulatory and antineoplastic components in RS1314.…”