Metabolite Profile of Salidroside in Rats by Ultraperformance Liquid Chromatography Coupled with Quadrupole Time-of-Flight Mass Spectrometry and High-Performance Liquid Chromatography Coupled with Quadrupole-Linear Ion Trap Mass Spectrometry

Abstract

In the present work, the salidroside metabolite profile in rat urine was investigated, and subsequently the metabolic pathways of salidroside were proposed. After administrations of salidroside at an oral dose of 100 or 500 mg/kg, rat urine samples were collected and pretreated with methanol to precipitate the proteins. The pretreated samples were analyzed by an Acquity ultraperformance liquid chromatography (UPLC) coupled with an HSS T3 column and detected by quadrupole time-of-flight mass spectrometry (Q-TOF-MS) or high-performance liquid chromatography coupled with hybrid triple-quadrupole linear ion trap mass spectrometry (HPLC/Q-trap-MS). A total of eight metabolites were detected and identified on the basis of the characteristics of their protonated ions in the urine samples. The results elucidated that salidroside was metabolized via glucuronidation, sulfation, deglycosylation, hydroxylation, methylation, and dehydroxylation pathways in vivo.

Phenylethanoid Glycosides: Research Advances in Their Phytochemistry, Pharmacological Activity and Pharmacokinetics

“…administration, whereas it may be further metabolized to other metabolites, and resulted in undetectable p-tyrosol in the plasma sample [138]. The speculation was verified by Hu's experiment, in which 123 and its deglycosylation phase I metabolite p-tyrosol were further metabolized to glucuronidation and sulfation products and mainly excreted through the urine excretion pathway [139]. Later, Guo's research team studied the metabolism of 123 and p-tyrosol in liver tissues after i.v.…”

“…What's more, simultaneous determination of more than one chemical marker and their pharmacokinetic studies were also reported. The microemulsion liquid chromatography (MELC) method [136] and the two-phase hollow fiber liquid phase microextraction coupled with a magnetofluid technique [137] for simultaneous determination of 117, 120, 121 and tubuloside B (139) in rat plasma after oral administration of Cistanche salsa extract by HPLC were developed. In the MELC method, the calibration curve for the four PhGs was linear in the range of 10-1000 ng/mL with the correlation coefficients greater than 0.9994.…”

Cytosolic β-glucosidase inhibition and renal blood flow suppression are leading causes for the enhanced systemic exposure of salidroside in hypoxic rats

“…p-Tyrosol sulfate was the predominant metabolite identied in the hepatic metabolism of SAL, which accounted for over 50% of the total metabolites in systemic circulation. 10,11 The formation rate of p-tyrosol sulfate could therefore serve as an indicator for the hepatic metabolic rate of SAL. The liver S9 fraction (RLS) derived from 5 normoxic rats and 5 hypoxic rats were prepared respectively according to previously mentioned method.…”

“…7a and b). 10,11 It was noticed that the formations of p-tyrosol sulfate were only dramatically inhibited when SAL was incubated with RLS in the presence of CBG inhibitor, suggesting the potential roles of CBG in the deglycosylation of SAL in rats. Moreover, the formations of p-tyrosol sulfate were signicantly inhibited when p-tyrosol was incubated with RLS in the presence of SULT2A1 inhibitor, suggesting the potential roles of SULT2A1 in the sulfation of SAL in rats.…”

“…1c) in systemic circulation turns out to be the sulfate form of SAL aglycone (p-tyrosol). 10,11 There are indeed speculations suggesting that hypoxia alters pharmacokinetics of some drug by suppressing the cytochrome P450 (CYP) enzymes, but the effect of hypoxia on SGLT1, glycosidase and sulfotransferase (SULT) has never been explored. 12 Since about 20% of administered SAL is excreted from urine in the form of parent compound, whether hypoxia alters the renal function of rats also deserve further investigation.…”