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      Development of Validated Methods and Quantification of Curcuminoids and Curcumin Metabolites and Their Pharmacokinetic Study of Oral Administration of Complete Natural Turmeric Formulation (Cureit™) in Human Plasma via UPLC/ESI-Q-TOF-MS Spectrometry

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          Abstract

          Specific and sensitive ultra-high performance liquid chromatography-quadrupole time of flight-mass spectroscopy (UPLC-QTOF-MS) methods have been developed for the determination of curcuminoids and curcumin metabolites in human blood plasma. The UPLC-QTOF-MS method used a binary solvent delivery system and the chromatographic separation was performed on a C-18 (2.1 × 50 mm; 1.7 µm) column. Mass spectra were obtained on a Waters Xevo G2S Q-TOF mass spectrometer. The developed methods to characterize the pharmacokinetics of curcuminoids and curcumin metabolites in human blood plasma after an oral administration of bioavailable curcumin—Cureit™—were validated. It was found that the complete turmeric matrix enhances the concentration of tetrahydrocurcumin (THC), hexahydrocurcumin (HHC), octahydrocurcumin (OHC), curcumin- O-glucuronide (COG) and curcumin- O-sulfate (COS) in the blood plasma once the product is administrated.

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          The revision of the Declaration of Helsinki: past, present and future.

          Robert V Carlson, Kenneth M Boyd, David J Webb (2004)
          The World Medical Association's Declaration of Helsinki was first adopted in 1964. In its 40-year lifetime the Declaration has been revised five times and has risen to a position of prominence as a guiding statement of ethical principles for doctors involved in medical research. The most recent revision, however, has resulted in considerable controversy, particularly in the area of the ethical requirements surrounding placebo-controlled trials and the question of responsibilities to research participants at the end of a study. This review considers the past versions of the Declaration of Helsinki and asks the question: How exactly has the text of the Declaration changed throughout its lifetime? Regarding the present form of the Declaration of Helsinki we ask: What are the major changes in the most recent revision and what are the controversies surrounding them? Finally, building on the detailed review of the past and present versions of the Declaration of Helsinki, we give consideration to some of the possible future trajectories for the Declaration in the light of its history and standing in the world of the ethics of medical research.
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            Curcumin is a potent DNA hypomethylation agent.

            Zhongfa Liu, Zhiliang Xie, William Jones … (2009)
            Molecular docking of the interaction of curcumin and DNMT1 suggested that curcumin covalently blocks the catalytic thiolate of C1226 of DNMT1 to exert its inhibitory effect. This was validated by showing that curcumin inhibits the activity of M. SssI with an IC(50) of 30 nM, but no inhibitory activity of hexahydrocurcumin up to 100 microM. In addition, curcumin can induce global DNA hypomethylation in a leukemia cell line.
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              Enhancement of curcumin oral absorption and pharmacokinetics of curcuminoids and curcumin metabolites in mice.

              Chang-Han Chen, Tina W F Yen, Lisa Yee … (2012)
              Curcumin has shown a variety of biological activity for various human diseases including cancer in preclinical setting. Its poor oral bioavailability poses significant pharmacological barriers to its clinical application. Here, we established a practical nano-emulsion curcumin (NEC) containing up to 20% curcumin (w/w) and conducted the pharmacokinetics of curcuminoids and curcumin metabolites in mice. This high loading NEC was formulated based on the high solubility of curcumin in polyethylene glycols (PEGs) and the synergistic enhancement of curcumin absorption by PEGs and Cremophor EL. The pharmacokinetics of curcuminoids and curcumin metabolites was characterized in mice using a LC-MS/MS method, and the pharmacokinetic parameters were determined using WinNonlin computer software. A tenfold increase in the AUC (0→24h) and more than 40-fold increase in the C (max) in mice were observed after an oral dose of NEC compared with suspension curcumin in 1% methylcellulose. The plasma pharmacokinetics of its two natural congeners, demethoxycurcumin and bisdemethoxycurcumin, and three metabolites, tetrahydrocurcumin (THC), curcumin-O-glucuronide, and curcumin-O-sulfate, was characterized for the first time in mice after an oral dose of NEC. This oral absorption enhanced NEC may provide a practical formulation to conduct the correlative study of the PK of curcuminoids and their pharmacodynamics, e.g., hypomethylation activity in vivo.
              Article 0 comments Cited 46 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-ta): Molecules
                Journal ID (iso-abbrev): Molecules
                Journal ID (publisher-id): molecules
                Title: Molecules : A Journal of Synthetic Chemistry and Natural Product Chemistry
                Publisher: MDPI
                ISSN (Electronic): 1420-3049
                Publication date (Electronic): 20 September 2018
                Publication date Collection: October 2018
                Volume: 23
                Issue: 10
                Electronic Location Identifier: 2415
                Affiliations
                [1 ]R&D Centre, Aurea Biolabs (P) Ltd., Kolenchery, Cochin-Kerala 682311, India; shintu.jude@ 123456plantlipids.com (S.J.); amalraj.a@ 123456plantlipids.com (A.A.)
                [2 ]Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati, Assam-781039, India; kunnumakkara@ 123456iitg.ernet.in
                [3 ]#2/5, Dahlia Building, 3rd Floor, 80 Feet Road, RMV 2nd Stage, Bengaluru, Karnataka 560094, India; divya@ 123456bioagiletherapeutics.com
                [4 ]Institute of Mitochondrial Medicine, Pfalzburger Str. 43/44, 10717 Berlin, Germany; loeffler@ 123456imm.institute
                Author notes
                [* ]Correspondence: sreeraj.gopi@ 123456plantlipids.com ; Tel.: +91-974-599-9042
                Author information
                https://orcid.org/0000-0003-0126-1539
                Article
                Publisher ID: molecules-23-02415
                DOI: 10.3390/molecules23102415
                PMC ID: 6222699
                PubMed ID: 30241377
                SO-VID: f31bc1b7-eaf9-4728-ae87-b729ffcf22f0
                Copyright © © 2018 by the authors.
                License:

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                Date received : 27 August 2018
                Date accepted : 15 September 2018
                Categories
                Subject: Article

                Keywords: curcuminoids,curcumin metabolites,uplc/esi-q-tof-ms spectrometry,pharmacokinetic,bioavailable curcumin (cureit™)
                Data availability:
                Keywords: curcuminoids, curcumin metabolites, uplc/esi-q-tof-ms spectrometry, pharmacokinetic, bioavailable curcumin (cureit™)

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