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Quantitative Analysis of Estrogenic Xenobiotics in Humans Using Liquid Chromatography-Mass Spectrometry

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posted on 11.06.2014 by Yang Yuan
Women are trying botanical dietary supplements for the possible relief of menopausal symptoms as alternatives to conventional HRT. Standardization of a botanical dietary supplement is an essential step to achieve a safe and reliable product. Typically, chemical standardization is used to provide consistent levels of active constituents and predictable pharmacological effects to consumers. Humulus lupulus L. (hops) is a source of prenylated flavonoids, and hop dietary supplements are often standardized to the phytoestrogen 8-prenylnaringenin. In this dissertation, a HPLC-MS-MS method is described and validated for the standardization of a hop extract, which was used for a Phase I clinical trial. To determine if prenylflavonoids from a standardized hop extract are orally bioavailable, a Phase I clinical trial was carried out. Five menopausal women subjects were recruited and received 3 escalating dosages of the hop extract with a one-month washout period between each dosage. Using a newly developed and validated UHPLC-MS-MS method that was approximately 10-fold faster than the HPLC-MS-MS method used to standardize the hop extract, serum and urine levels of prenylflavonoids from hops were determined. These prenylflavonoids included xanthohumol, isoxanthohumol, 8-prenylnaringenin, and 6-prenylnaringenin. These data suggest that hop prenylflavonoids are absorbed rapidly after oral administration and that the major circulating forms are glucuronic acid conjugates. Bisphenol A (BPA) is used as a material for the production of epoxy resins and polycarbonate plastics. BPA has been reported to migrate from can surface coatings and polycarbonate plastics into food and water. A sensitive, selective and rapid analytical method based on UHPLC-MS-MS was developed and validated for the measurement of BPA and its primary metabolite, BPA-glucuronide, in human serum.

History

Advisor

van Breemen, Richard B.

Department

Medicinal Chemistry and Pharmacognosy

Degree Grantor

University of Illinois at Chicago

Degree Level

Doctoral

Committee Member

Fitzloff, John F. Murphy, Brian T. Franzblau, Scott G. Prins, Gail S.

Submitted date

2012-08

Language

en

Issue date

10/12/2012

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