Structural elucidation ofin vitrometabolites of bavachinin in rat liver microsomes by LC-ESI-MSⁿand chemical synthesis

Abstract

1. Bavachinin isolated from Psoralea corylifolia has various activities, such as antimicrobial, antiallergic, antitumor and so on. Our previous study showed that natural bavachinin exhibits peroxisome proliferator-activated receptor γ-agonist activity. 2. In vitro studies on bavachinin metabolism were conducted using rat liver microsomes incubated at 37 °C for 60 min. 3. Structures of eight metabolites of the incubation mixtures were cautiously characterized using electrospray tandem mass spectra and three synthetic compounds. The results indicated that eight metabolites of bavachinin were biotransformed mainly through oxidation. 4. The metabolic pathways of bavachinin were elucidated in vitro. These results contribute to the understanding of bavachinin's in vivo metabolism.

Pharmacokinetic and metabolism studies of bavachinin through ultra‐high‐performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry

“…To determine the fragmentation patterns of BVC that determine the structure of metabolites, a reference compound of BVC was acquired for the target product with relatively high collision in UPLC‐Q/TOF‐MS. As shown in Figure S2, BVC generated a protonated ion [M + H] + at m / z 339.1599 in the positive ion mode, and a series of fragment ions at m / z 283.0970, 271.0971, 219.1027, 189.0552, 177.0551 and 147.0445, which was consistent with the result described in our previous study (Xie et al, ).…”

“…Their MS fragmentation patterns are similar, with a typical fragment ion at m / z 283.0968 signifying that hydroxylation occurs in the prenyl group. This type of isometry has also been detected in our previous in vitro studies (Ma et al, ; Xie et al, ) and another study (Guo, Nikolic, Chadwick, Pauli, & van Breemen, ). Hence, M7–1 and M7–2 may be cis–trans isomers in which hydroxyl groups are added to the 4′′ and 5′′ positions of the isopentenyl group, respectively.…”

“…M7-1 and M7-2 were eluted at 5.18 and 5.25 min with the also been detected in our previous in vitro studies (Ma et al, 2015;Xie et al, 2016) and another study (Guo, Nikolic, Chadwick, Pauli, & van Breemen, 2006). Hence, M7-1 and M7-2 may be cis-trans isomers in which hydroxyl groups are added to the 4′′ and 5′′ positions of the isopentenyl group, respectively.…”

“…There were five metabolites connected with isomerization, suggesting that isomerization was notable in metabolism. Of the eight in vitro metabolites (only Phase I) found in our previous study (Xie et al, ), two were found ( M7–1 , M7–2 ), and the other six, concerning hydroxylation and reduction, were undetected. A possible reason for this was that the metabolic enzymes from the in vitro metabolism experiment were excessive, whereas in vivo , a possible competitive relationship might lead to an undetected quantity.…”

“…To our knowledge, there are few reports on the absorption, distribution, metabolism and excretion of BVC in vivo . Our previous report is the only one regarding its phase I metabolism in vitro (Xie et al, ). Quantitative information on BVC in biological samples is insufficient.…”