Simultaneous Determination of Chlorogenic Acid Isomers and Metabolites in Rat Plasma Using LC-MS/MS and Its Application to A Pharmacokinetic Study Following Oral Administration of Stauntonia Hexaphylla Leaf Extract (YRA-1909) to Rats

Abstract

Stauntonia hexaphylla leaf extract (YRA-1909), which is widely used for the antirheumatic properties, has been under phase 2 clinical trials in patients with rheumatoid arthritis since April 2017. Liquid chromatography-tandem mass spectrometric method while using liquid–liquid extraction with ethyl acetate was validated for the simultaneous determination of the major active components of YRA-1909, including chlorogenic acid (CGA), neochlorogenic acid (NCGA), cryptochlorogenic acid (CCGA), and their metabolites (i.e., caffeic acid (CA), caffeic acid 3-O-glucuronide (CA-3-G), caffeic acid 4-O-glucuronide (CA-4-G), and ferulic acid (FA)) in rat plasma and applied to a pharmacokinetic study of YRA-1909 in rats. Seven analytes were separated on Halo C18 while using gradient elution of formic acid and methanol, and then quantified in selected reaction monitoring mode whle using negative electrospray ionization. Following oral administration of YRA-1909 at doses of 25, 50, and 100 mg/kg to male Sprague-Dawley rats, CGA, NCGA, and CCGA were rapidly absorbed and metabolized to CA, CA-3-G, and CA-4-G. The area under the plasma concentration-time curve (AUClast) of CGA, NCGA, CCGA, and three metabolites linearly increased as the YRA-1909 dose increased. Other pharmacokinetic parameters were comparable among three doses studied. AUClast values for CA, CA-3-G, and CA-4-G exceeded those for CGA, NCGA, and CCGA.

Analysis of phenolic acids and flavonoids in leaves of Lycium barbarum from different habitats by ultra‐high‐performance liquid chromatography coupled with triple quadrupole tandem mass spectrometry

“…Finally, ferulic acid lost a methyl group, as well as a CO 2 , in ESI − mode. The ion transitions above were same as the literature (Ahmad et al, ; Chang et al, ; Choi et al, ; He et al, ; Li et al, ; Zhou et al, ).…”

Simultaneous determination of eight bioactive components in Marsdenia tenacissima extract in rat plasma by LC–MS/MS and its application in a pharmacokinetic study

“…Such a finding was ascribed to the low content and poor absorption in M. tenacissima extract. The caffeic acid content in M. tenacissima etract was the least, but its AUC 0– t value (2886.73 ± 93.27 ng h/ml) was higher than those of cryptochlorogenic acid, neochlorogenic acid and chlorogenic acid, which might be related to the absorption of cryptochlorogenic acid, neochlorogenic acid and chlorogenic acid by passive diffusion and the hydrolysis into caffeic acid by gastric esterase (Choi et al, 2018). In addition, the administration dosage of tenacissoside H in M. tenacissima extract was lower than that of tenacissoside G, but the C max and AUC 0– t values were significantly higher than that of tenacissoside G, which demonstrated that the intestinal absorption of tenacissoside H may be significantly higher than that of tenacissoside G. The rank order of C max of neochlorogenic acid, chlorogenic acid, tenacissoside B, I and G corresponded to their administration dosages in rats.…”

Pharmacokinetics study of 16 active ingredients from Tabson‐2 decoction in normal and d‐galactose induced osteoporosis rats by liquid chromatography–tandem mass spectrometry

“…The C max and AUC of GA in control group was much higher than those of PA, and the C max, AUC of CCGA, NCGA, and CGA was with distinct value as well. The low exposure of CCGA and CGA was reportedly related to their low bioavailability and urinary recovery [26]. Moreover, the mutual transformation in the body could be another reason for the different exposure of these isomers [27].…”