15 Methods of Analysis and Separation of Chiral Flavonoids

Journal of Chromatography B, 848 (2007) 159181

Review

Methods of analysis and separation of chiral flavonoids

Abstract

Althoughwithin the puses, plant ppharmacodyseparation oused to sepa 2006 Else

Keywords: F

Contents

1. Introd2. Chrom

2.1.

2.2.2.3.2.4.

3. Flavan3.1.3.2.3.3.3.4.3.5.3.6.3.7.3.8.3.9.3.10.3.11.3.12.

CorresponE-mail add

1570-0232/$ doi:10.1016/j.uction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 160atographic methods of separation of enantiomers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 161Direct methods of analysis: chiral stationary phases (CSP) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1622.1.1. Chiral polymer phases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1622.1.2. Chiral mobile phase additives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 172Indirect method of analysis: chiral derivatization techniques . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 173Racemization, enantiomerization and epimerization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 173Advantages and disadvantages of current methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 174ones . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 175Dihydrowogonin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 175Dihydrooroxylin A . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 175Eriocitrin and eriodictyol . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 175Flavanone . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 175Hesperidin and hesperetin. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 176Homoeriodictyol . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 176Hydroxyflavanone, 2- . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 177Hydroxyflavanone, 4- . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 177Hydroxyflavanone, 6- . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 177

Isosakuranetin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 177Liquiritigenin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 177Methoxyflavanone, 4- . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 177

ding author. Tel.: +1 509 335 4754; fax: +1 509 335 5902.ress: [email protected] (N.M. Davies).

see front matter 2006 Elsevier B.V. All rights reserved.jchromb.2006.10.052Jaime A. Yanez a, Preston K. Andrews b, Neal M. Davies a,a College of Pharmacy, Department of Pharmaceutical Sciences and Pharmacology and Toxicology Graduate Program,

Washington State University, Pullman, Washington 99164-6534, USAb Department of Horticulture and Landscape Architecture, Washington State University, Pullman, Washington 99164-6534, USA

Received 29 April 2006; accepted 28 October 2006Available online 20 November 2006

the analysis of the enantiomers and epimers of chiral flavanones has been carried out for over 20 years, there often remains a deficitharmaceutical, agricultural, and medical sciences to address this issue. Hence, despite increased interest in the potential therapeutichysiology roles, and health-benefits of chiral flavanones, the importance of stereoselectivity in agricultural, nutrition, pharmacokinetic,namic, pharmacological activity and disposition has often been ignored. This review presents both the general principles that allowf chiral flavanones, and discusses both the advantages and disadvantages of the available chromatographic assay methods and proceduresrately quantify flavanone enantiomers and epimers in biological matrices.vier B.V. All rights reserved.

lavonoid; Flavanone; HPLC; Chiral; Enantiomer; Epimer

160 J.A. Yanez et al. / J. Chromatogr. B 848 (2007) 159181

3.13. Methoxyflavanone, 5- . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1773.14. Methoxyflavanone, 6- . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1773.15 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1773.16 . . . .3.17 . . . .3.18 . . . .3.19 . . . .3.20 . . . . .3.21 . . . . .3.22 . . . .3.23 . . . .

4. Con . . . .Ack . . . . .Refe . . . . .

1. Introd

In 1936substancetor in thesubstancesequentlyGyorgyisits isolatiomore thanstudied. Fof low mopyrone strclasses incanthocyantains a cosources ofand strawband tomatclasses offlavonoidsfruits [92tomatoesmint [26],thyme [25

Flavon70 yearsshown toin somehave been also shown to exhibit beneficial effects on cap-illary peanti-plateanti-hype[3,10,30,3[30], cytinflammaanti-hepa

In addpresent a utinguishesthe flavanconfigura

linkatones

ve twflavaharidycosositenicvastfrom

s rac

ers)ure flctyols, Swmeseure oted aany (I Inteas thiego

Genimp

ic flayea

of a,59

stationary phases [6372]. There is a paucity of investigations

rmeability and fragility [3,10,31,3441], to havelet [3,10,30,31,3440], hypolipidemic [30,4245],rtensive [14,30,46], anti-microbial [30], anti-viral1,3440,47,48], anti-allergenic [49], anti-ulcerogenic

otoxic [30], anti-neoplastic [9,12,30,5055], anti-tory [3,10,30,31,3440], anti-atherogenic [30,56], andtotoxic [30] activities.ition, within the large family of flavonoids, flavanonesnique structural feature known as chirality, which dis-them from all other classes of flavonoids (Fig. 1). All

ones have a chemical structure based on a C6C3C6tion consisting of two aromatic rings joined by a three-

detailing the importance of stereospecific pharmacokinetics andpharmacodynamics of chiral flavanones. Of these investigations,only one reports the human urinary excretion of four differ-ent flavanones (liquiritigenin, naringenin, dihydrowogonin, anddihydrooroxylin A) after ingestion of different herbal products[62,73,74], unfortunately pharmacokinetics analysis and mod-eling were not employed.

It is important to consider that it has been reported that somechiral flavanones are stereochemically unstable depending onthe substitution pattern of various functional groups around thestereogenic center. When inversion occurs causing the formationof a racemate it is termed racemization, while enantiomerization. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 177

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 178

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 179

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 179. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 179

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 179. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 179. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 179. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 179. . . . . . . . . . . . . . . . . . . . . .