Simultaneous Chiral Separation of Flavanone, Naringenin, and Hesperetin Enantiomers by RP‐UHPLC‐DAD

Abstract

A rapid and effective RP-UHPLC-DAD method for enantioseparation of three flavanones, i.e., flavanone, naringenin, and hesperetin, was developed and validated. Chromatographic separation of the analytes was performed using a Chiralpak AD-3R analytical column under reverse phase conditions with methanol as the mobile phase. The method was validated in the concentration range of 0.2 to 50 µg/mL for enantiomers of flavanone and 0.5 to 50 µg/mL for enantiomers of naringenin and hesperetin. The limits of quantification were between 0.03 to 0.5 µg/mL. Intraday and interday precision were below 14% and accuracy varied from 0.04 to 8.17%.

Site-specific oxidation of flavanone and flavone by cytochrome P450 2A6 in human liver microsomes

“…Commercial preparation of racemic flavanone contains ( 2R )- and ( 2S )-enantiomers (Si-Ahmed et al, 2010; Baranowska et al, 2016). Studies of the molecular interaction of these flavanone enantiomers with the active sites of CYP2A6.1 indicated that the C2´ atom of the ( 2R )-isomer was located nearer (distance 3.8Å) the iron center of CYP2A6 (2FDY) as compared with the ( 2S )-isomer (distance 6.9Å), while C6 of ( 2S )-flavanone was more closely located to the iron center of CYP2A6 than that of (2R)-isomer (Figure 11).…”

“…Flavanone [a racemic mixture of ( 2R )- and ( 2S )-enantiomers] (Akashi et al, 1998; Si-Ahmed et al, 2010; Baranowska et al, 2016), flavone, 5-, 6-, and 7-hydroxyflavone (5OHF, 6OHF, and 7OHF), 5,7- and 7,8-dihydroxyflavone (57diOHF and 78diOHF), 5-, 6- and 7-hydroxyflavanone (5OHFva, 6OHFva and 7OHFva), α -naphthoflavone (ANF), coumarin, and N , N ´, N ´´-triethylenethiophosphoramide (thio-TEPA) were obtained from Sigma-Aldrich (St. Louis, MO, USA) and Wako Pure Chemicals (Osaka, Japan). 2´-, 3´-, and 4´-Hydroxyflavanone (2´OHFva, 3´OHFva, and 4´OHFva) were purchased from Tokyo Kasei Co. (Tokyo).…”

“…We recently reported that racemic flavanone, consisting of its ( 2R )- and ( 2S )-enantiomers (Akashi et al, 1998; Si-Ahmed et al, 2010; Baranowska et al, 2016), is oxidized by human P450 enzymes to form at least eight mono-hydroxylated flavanones, three mono-hydroxylated flavones, and flavone (Figure 1) (Kakimoto et al, 2018). Among eight recombinant human P450 enzymes examined, CYP2A6 was the most active in oxidizing flavanone to form 2´- and 6-hydroxyflavanones and to form flavone.…”

Poloxamer-chitosan-based Naringenin nanoformulation used in brain targeting for the treatment of cerebral ischemia

“…We required an easy, less time consuming, sensitive, robust, as well as highly reproducible bioanalytical method for the quantification NRG in the brain and blood samples as per the evaluation of pharmacokinetic parameters. There are so many analytical methods are reported for the quantification of NRG but not a single bioanalytical method reported for brain or brain homogenate samples for the brain-PK including for the quantification of NRG as single analyte with high robust method (Sun et al, 2014, Wang et al, 2014, Magiera et al, 2012, Baranowska et al, 2016a, Baranowska et al, 2016b). The most important parameter for the estimation of NRG-bioanalytical method (upto nanogram i.e.…”

Chiral pillar[5]arene-functionalized silica microspheres: synthesis, characterization and enantiomer separation

“…To date, there have been many reports on CSPs such as polysaccharides, 21–23 macrocycles (crown ether, 24 cyclodextrins, 25,26 and calixarene 27 ) and other types of CSPs. 28 However, there are still some limitations for macrocyclic stationary phases including limited chiral sites, irregular structures, or poor separation effects.…”