title: Enantiospecific analysis of 8-prenylnaringenin in biological fluids by liquid-chromatography-electrospray ionization mass spectrometry: application to preclinical pharmacokinetic investigations.
abstract: 8-Prenylnaringenin (8PN) is a naturally occurring bioactive chiral prenylflavonoid found most commonly in the female flowers of hops (Humulus lupulus L.). A stereospecific method of analysis for 8PN in biological fluids is necessary to study the pharmacokinetic disposition of each enantiomer. A novel and simple liquid chromatographic-electrospray ionization-mass spectrometry (LC-ESI-MS) method was developed for the simultaneous determination of R- and S-8PN in rat serum and urine. Carbamazepine was used as the internal standard (IS). Enantiomeric resolution of 8PN was achieved on a Chiralpak(®) AD-RH column with an isocratic mobile phase consisting of 2-propanol and 10 mM ammonium formate (pH 8.5) (40:60, v/v) and a flow rate of 0.7 mL/min. Detection was achieved using negative selective ion monitoring (SIM) of 8PN at m/z 339.15 for both enantiomers and positive SIM m/z at 237.15 for the IS. The calibration curves for urine were linear over a range of 0.01-75 µg/mL and 0.05-75 µg/mL for serum with a limit of quantification of 0.05 µg/mL in serum and 0.01 µg/mL in urine. The method was successfully validated showing that it was sensitive, reproducible, and accurate for enantiospecific quantification of 8PN in biological matrices. The assay was successfully applied to a preliminary study of 8PN enantiomers in rat.
authors.affiliation: Faculty of Pharmacy, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Stephanie E
authors.initials: SE
authors.lastname: Martinez
authors.forename: Ted M
authors.initials: TM
authors.lastname: Lakowski
authors.forename: Neal M
authors.initials: NM
authors.lastname: Davies
mesh_terms: D000818:Animals; D001774:Blood Chemical Analysis / Q000379:methods*; D002853:Chromatography, Liquid / Q000379:methods*; D004355:Drug Stability; D044950:Flavanones / Q000097:blood / Q000737:chemistry* / Q000493:pharmacokinetics* / Q000652:urine; D057230:Limit of Detection; D016014:Linear Models; D008297:Male; D051381:Rats; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D013237:Stereoisomerism; D016482:Urinalysis / Q000379:methods*
chemical_list: C119737:8-prenylnaringenin; D044950:Flavanones
keywords: 8-Prenylnaringein; Humulus lupulus L; LC/MS; analysis; chiral; enantioseparation; enantiospecific; flavonoid; phytoestrogen; preclinical pharmacokinetics