Characterization of forsythoside A metabolites in rats by a combination of UHPLC‐LTQ‐Orbitrap mass spectrometer with multiple data processing techniques

Abstract

Forsythoside A (FTA), the main active constituent isolated from Fructus Forsythiae, has various biological functions including anti-oxidant, anti-viral and anti-microbial activities. However, while research on FTA has been mainly focused on the treatment of diseases on a material basis, FTA metabolites in vivo have not been comprehensively evaluated. Here, a rapid and sensitive method using a UHPLC-LTQ-Orbitrap mass spectrometer with multiple data processing techniques including high-resolution extracted ion chromatograms, multiple mass defect filters and diagnostic product ions was developed for the screening and identification of FTA metabolites in rats. As the result, a total of 43 metabolites were identified in biological samples including 42 metabolites in urine, 22 metabolites in plasma and 15 metabolites in feces. These results demonstrated that FTA underwent a series of in vivo metabolic reactions including methylation, dimethylation, sulfation, glucuronidation, diglucuronidation, cysteine conjugation and their composite reactions. The research enhanced our understanding of FTA metabolism and built a foundation for further toxicity and safety studies.

Therapeutic potential of phenylethanoid glycosides: A systematic review

“…213 Three metabolites of forsythiaside A (200 mg/kg, po) were identified in rats, with 42 in urine, 22 in plasma, and 15 in feces. 214 In general, forsythiaside A was mainly methylated, dimethylated, sulfated, glucuronidated, diglucuronidated, and cysteine conjugated. Hydroxyl group on caffeic acid of forsythiaside A was the major target metabolic site.…”

“…Hydroxyl group on caffeic acid of forsythiaside A was the major target metabolic site. 214 Sixty six metabolites of poliumoside (1000 mg/kg, po) in rat feces samples were identified. The metabolic pathways of poliumoside involving in phase I were hydroxylation, hydration, hydrolysis, methoxylation, dehydrogenation, and reduction; while the phase II reactions were sulfation, dimethylation, and acetylation.…”

“…In addition, acyl‐migration and acetylization of verbascoside (M17) produced isoverbascoside (M18) and acetyl‐verbascoside (M19) 213 . Three metabolites of forsythiaside A (200 mg/kg, po) were identified in rats, with 42 in urine, 22 in plasma, and 15 in feces 214 . In general, forsythiaside A was mainly methylated, dimethylated, sulfated, glucuronidated, diglucuronidated, and cysteine conjugated.…”

“…In general, forsythiaside A was mainly methylated, dimethylated, sulfated, glucuronidated, diglucuronidated, and cysteine conjugated. Hydroxyl group on caffeic acid of forsythiaside A was the major target metabolic site 214 . Sixty six metabolites of poliumoside (1000 mg/kg, po) in rat feces samples were identified.…”

A Comprehensive Screening and Identification of Genistin Metabolites in Rats Based on Multiple Metabolite Templates Combined with UHPLC-HRMS Analysis

“…In recent years, with the continuous development of Orbitrap technology, Orbitrap mass spectrometer is widely used in pharmaceutical analysis due to the HR detection through combining with the linear ion trap [ 17 , 18 , 19 ]. Nowadays, UHPLC-LTQ-Orbitrap mass spectrometer has been widely applied in metabolism studies [ 20 , 21 , 22 , 23 , 24 ].…”