Liquid chromatography with tandem mass spectrometry quantification of urinary proanthocyanin A2 dimer and its potential use as a biomarker of cranberry intake

Authors: WALSH, JASON - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; REN, XIAOBAI - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; ZAMPARIELLO, CARLY - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; POLASKY, DANIEL - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; MCKAY, DIANE - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; BLUMBERG, JEFFREY - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; CHEN, CHUNG-YEN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University

Submitted to: Journal of Separation Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/2/2015
Publication Date: 1/1/2016
Citation: Walsh, J.M., Ren, X., Zampariello, C., Polasky, D.A., Mckay, D.L., Blumberg, J.B., Chen, C. 2016. Liquid chromatography with tandem mass spectrometry quantification of urinary proanthocyanin A2 dimer and its potential use as a biomarker of cranberry intake. Journal of Separation Science. 39(2):342-349.

Interpretive Summary: Cranberries are rich in a variety of phenolic compounds, including flavonoids, tannins, anthocyanins, and proanthocyanins (PACs). These phenolic compounds are prevalent in fruits, vegetables, whole grains, and spices. Further, their consumptions have been linked to reduced risk for chronic diseases, such as heart disease and cancers, via actions to clean up free radicals and reduce inflammation. Consumption of cranberries is associated with the reduction in risk of urinary tract infections, ulcers, and tooth decay. The underlying mechanisms responsible for these and other potential benefits include antibacterial, antiviral, and antioxidant activities. PACs are oligomeric flavonoids and present abundantly in cranberries. Most importantly, these compounds were found to be associated with a reduced risk of recurrent urinary tract infections by inhibiting Escherichia coli adhesion to the wall of urinary tract. However, interpreting the varied results of human studies is confounded by lack of a valid biomarker(s) of their consumption. Here, we describe a sensitive analytical method for the quantification of urinary PAC from human subjects and test if this measure can serve as a biomarker for the consumption of cranberry juice. In this study, we established a reliable, sensitive analytical method for the quantification of cranberry PAC in human urine. However, we found in a small-scale human study that the urinary concentration of PAC is not likely to be a validated biomarker of cranberry intake.

Technical Abstract: The lack of a biomarker for the consumption of cranberries has confounded the interpretation of several studies investigating the effect of cranberry products, especially juices, on health outcomes. The objectives of this pilot study were to develop a liquid chromatography tandem mass spectrometric method for the quantification of the proanthocyanin dimer A-2 in human urine and validate urinary proanthocyanin dimer A-2 as a biomarker of cranberry intake. Five healthy, nonsmoking, premenopausal women (20-30 years of age, body mass index: 18.5-25 kg/m2) were assigned to consume a cranberry beverage containing 140 mg proanthocyanin and 35 kilocalories at 237 mL/day, according to a weekly dosing schedule for 7 weeks. Eleven 24 h and morning spot urine samples each were collected from each subject. A reliable, sensitive method for the detection of proanthocyanin dimer A-2 in urine using liquid chromatography with tandem mass spectrometry was developed with a limit of quantitation of 0.25 ng/mL and a relative standard deviation of 7.26%, precision of 5.7%, and accuracy of 91.7%. While proanthocyanin dimer A-2 was quantifiable in urine, it did not appear to be excreted in a concentration that corresponded to the dosing schedule and intake of cranberry juice. This article is protected by copyright. All rights reserved.