PMID- 37267874
OWN - NLM
STAT- MEDLINE
DCOM- 20230612
LR  - 20230612
IS  - 1873-264X (Electronic)
IS  - 0731-7085 (Linking)
VI  - 233
DP  - 2023 Sep 5
TI  - Development of a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method 
      for characterizing pomegranate extract pharmacokinetics in humans.
PG  - 115477
LID - S0731-7085(23)00246-7 [pii]
LID - 10.1016/j.jpba.2023.115477 [doi]
AB  - Pomegranate extracts standardized to punicalagins are a rich source of 
      ellagitannins including ellagic acid (EA). Recent evidence suggests that gut 
      microbiota-derived urolithin (Uro) metabolites of ellagitannins are 
      pharmacologically active. Studies have evaluated the pharmacokinetics of EA, 
      however, little is known about the disposition of urolithin metabolites 
      (urolithin A (UA) and B (UB)). To address this gap, we developed and applied a 
      novel ultra-high performance liquid chromatography-tandem mass spectrometry 
      (UHPLC-MS/MS) assay for the characterization of EA and Uro oral pharmacokinetics 
      in humans. Subjects (10/cohort) received a single oral dose (250 or 1000 mg) of 
      pomegranate extract (Pomella(R) extract) standardized to contain not less than 30 % 
      punicalagins, < 5 % EA, and not less than 50 % polyphenols. Plasma samples, 
      collected over 48 h, were treated with beta-glucuronidase and sulfatase to permit 
      comparison between unconjugated and conjugated forms of EA, UA and UB. EA and 
      urolithins were separated by gradient elution (acetonitrile/water, 0.1 % formic 
      acid) using a C(18) column connected to a triple quadrupole mass spectrometer 
      operating in the negative mode. Conjugated EA exposure was  approximately 5-8-fold higher than 
      unconjugated EA for both dose groups. Conjugated UA was readily detectable 
      beginning  approximately 8 h post-dosing, however, unconjugated UA was detectable in only a few 
      subjects. Neither form of UB was detected. Together these data indicate EA is 
      rapidly absorbed and conjugated following oral administration of Pomella(R) 
      extract. Moreover, UA's delayed appearance in the blood, primarily in the 
      conjugated form, is consistent with gut microbiota-mediated metabolism of EA to 
      UA, which is then rapidly converted to its conjugated form.
CI  - Copyright (c) 2023. Published by Elsevier B.V.
FAU - Wang, Yan-Hong
AU  - Wang YH
AD  - The National Center for Natural Products Research, University of Mississippi, 
      Oxford, MS, USA.
FAU - Mondal, Goutam
AU  - Mondal G
AD  - The National Center for Natural Products Research, University of Mississippi, 
      Oxford, MS, USA.
FAU - Khan, Washim
AU  - Khan W
AD  - The National Center for Natural Products Research, University of Mississippi, 
      Oxford, MS, USA.
FAU - Gurley, Bill J
AU  - Gurley BJ
AD  - The National Center for Natural Products Research, University of Mississippi, 
      Oxford, MS, USA.
FAU - Yates, Charles R
AU  - Yates CR
AD  - The National Center for Natural Products Research, University of Mississippi, 
      Oxford, MS, USA. Electronic address: cryates2@olemiss.edu.
LA  - eng
PT  - Journal Article
DEP - 20230523
PL  - England
TA  - J Pharm Biomed Anal
JT  - Journal of pharmaceutical and biomedical analysis
JID - 8309336
RN  - 65995-63-3 (punicalagin)
RN  - 0 (Hydrolyzable Tannins)
RN  - 19YRN3ZS9P (Ellagic Acid)
RN  - 0 (Plant Extracts)
SB  - IM
MH  - Humans
MH  - Chromatography, Liquid
MH  - *Tandem Mass Spectrometry
MH  - Hydrolyzable Tannins/metabolism
MH  - *Pomegranate
MH  - Chromatography, High Pressure Liquid
MH  - Ellagic Acid
MH  - Plant Extracts
OTO - NOTNLM
OT  - And human pharmacokinetics
OT  - Ellagic acid
OT  - Pomegranate
OT  - Punicalagins
OT  - UHPLC-MS/MS
OT  - Urolithin
COIS- Declaration of Competing Interest The authors declare the following financial 
      interests/personal relationships which may be considered as potential competing 
      interests: Charles Ryan Yates reports financial support was provided by Verdure 
      Sciences.
EDAT- 2023/06/03 11:41
MHDA- 2023/06/12 06:42
CRDT- 2023/06/02 18:09
PHST- 2022/12/24 00:00 [received]
PHST- 2023/05/18 00:00 [revised]
PHST- 2023/05/20 00:00 [accepted]
PHST- 2023/06/12 06:42 [medline]
PHST- 2023/06/03 11:41 [pubmed]
PHST- 2023/06/02 18:09 [entrez]
AID - S0731-7085(23)00246-7 [pii]
AID - 10.1016/j.jpba.2023.115477 [doi]
PST - ppublish
SO  - J Pharm Biomed Anal. 2023 Sep 5;233:115477. doi: 10.1016/j.jpba.2023.115477. Epub 
      2023 May 23.