Determination of α-hederin in rat plasma using liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) and its application to a pharmacokinetic study

Abstract

The evaluation of efficacy and safety should be paralleled with the assessment of comprehensive pharmacokinetic (PK) properties for a drug candidate, and a robust bioanalytical method is a prerequisite for obtaining PK information. a-Hederin is reported to have various in vitro and in vivo activities; however, very little is known about its PK and metabolic characteristics. In this study, we have developed an efficient LC-ESI(À)-MS/MS assay for a-hederin and its sapogenin hederagenin in rat plasma. Sample cleanup involved methanol precipitation for identification analysis and liquid-liquid extraction with ethyl acetate for quantification assay. LC analysis was performed under reversed-phase conditions in the modified "pulse gradient elution" mode. Analyte identification and quantification were conducted using multiple reaction monitoring (MRM) mode with euscaphic acid as the internal standard. Under these conditions, deglycosylated metabolites and their sulfate conjugates were detected; however, hederagenin was not detected in rat plasma samples after both oral and intravenous treatments. The mean plasma clearance (CL), volume of distribution (V SS ) and elimination half-life (t 1/2 ) of a-hederin were 0.24 L h À1 kg À1 , 0.25 L kg À1 and 2.67 h, respectively. The oral bioavailability (F) of a-hederin in rats was about 0.14%, which might result from the poor intestinal absorption and/or extensive biliary excretion. It is hoped that this validated method will be useful for future PK studies of a-hederin.

Pharmacokinetic parameters of three active ingredients hederacoside C, hederacoside D, and ɑ‐hederin in Hedera helix in rats

“…Kim et al determined hederacoside C in rats after oral and intravenous administration of hederacoside C with a validated LC-MS/MS method [16]. Li et al determined ɑ-hederin in rats after oral and intravenous administration of ɑ-hederin with a validated LC-ESI-MS/MS method [17]. However, in view of the pattern of the combined effects of several active ingredients for herb medicine, it is not plausible to trace the pharmacological activity of Hedera helix back to one single ingredient.…”

UHPLC‐Q‐TOF‐MS/MS Dereplication to Identify Chemical Constituents of Hedera helix Leaves in Vietnam

“…At T R = 25.24, compound 42 showed the formula of C 30 H 48 O 4 ([M-H] − at m / z 471.3488) and fragmented into ion at m / z 393. Comparing the MS/MS spectrum and data with the result of Hai-Long et al [ 26 ], compound 42 was characterized as hederagenin.…”

A Triterpenoid Having Anticancer Activity Found in Stem Bark of Holoptelea integrifolia (Roxb.) Planch

“…Compound (1) gave second largest fragment peak at m/z 472 [M (saligcinnamide)-H 2 O] + or due to presence of hederagenin (molecular mass 472). Hederagenin showed characteristic fragment ions peaks at m/z 471.3, 405.2, and 393.3 [12] which were not matched with the fragment ions of the compound (1). When third largest fragment peak of (1) at m/z 456 was taken as a molecular ion peak [M] + , it was found similar to the molecular ion peak of Betulinic acid, oleanolic acid, and ursolic acid with molecular formula C 30 H 48 O 3 .When mass spectrum of these compounds [13] were compared with the mass spectra of (1) they were almost found identical.…”

“…Pooled fractions (10 and 11) were re-chromatographed with chloroform to get 1-40 fractions. Similar fractions (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13) and (14-40) were pooled. Fraction (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13) was re-chromatographed with chloroform to get 1-38 fractions.…”

“…Similar fractions (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13) and (14-40) were pooled. Fraction (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13) was re-chromatographed with chloroform to get 1-38 fractions. Similar fractions (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20) were pooled and combined with previous left-over fractions (14-40) (isocratic) and subjected to CC with chloroform to get fractions (1-23).…”