A high-throughput quantification method of curcuminoids and curcumin metabolites in human plasma via high-performance liquid chromatography/tandem mass spectrometry
Open accessAbstract
Curcuminoids, a mixture of curcumin, demethoxycurcumin (DMC), and bisdemethoxycurcumin (BDMC), have shown a variety of clinical benefits for several human chronic diseases including osteoarthritis, rheumatoarthritis, and type II diabetes. However, the oral bioavailability of curcumin is extremely low due to its avid metabolism to curcumin O-glucuronide (COG), curcumin O-sulfate (COS), tetrahydrocurcumin (THC), and other minor metabolites. This paper reports a unique liquid chromatography/tandem mass spectrometry (LC-MS/MS) method to quantify curcumin, DMC, BDMC, COG, COS, and THC simultaneously in human plasma. These compounds were extracted with ethyl acetate from human plasma, separated on a BetaBasic-8 column, and monitored on a triple quadruple mass spectrometer coupled with API electrospray under a negative ion mode. The linearity of these respective curcuminoids and curcumin metabolites was shown in the range of 2-1000ng/mL with 85-115% accuracy and ≤20% precision in human plasma. This method was validated according to the US FDA GLP analytic criteria and applied to characterize the pharmacokinetics of curcumin, COG, and COS in human plasma after an oral dose of bioavailable curcumin (nanoemulsion curcumin).
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Curcuminoids (CURs) are the principal ingredients of Curcuma longa L., an herbal plant used in east Asia to alleviate pain and inflammation.
“Analogues comprising curcumin, bisdemethoxycurcumin, demethoxycurcumin and cyclocurcumin are collectively referred to as curcuminoids (CURs) [12], which constitute the principal ingredients of CL—an herbal plant used in east Asia to alleviate pain and inflammation.”
From Efficacy and safety of curcuminoids alone in alleviating pain and dysfunction for knee osteoarthritis: a systematic review and meta-analysis of randomized controlled trials (2022) · cites this paper as [12]
The Introduction identifies curcumin, demethoxycurcumin, and bisdemethoxycurcumin as curcuminoids extracted from Curcuma longa, supporting part of the definition to which the citation is attached. It does not include cyclocurcumin in that definition or state that the plant was used in East Asia to alleviate pain and inflammation. (LLM, conf=0.86)
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Bioavailability of curcumin: Problems and promises
Anand, P., Kunnumakkara, A. B., Newman, R. A., & Aggarwal, B. B. (2007) · Molecular Pharmaceutics · doi:10.1021/mp700113r · Cited by 5,543 · see citing works
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Feng, J., Li, Z., Tian, L., Mu, P., Hu, Y., Xiong, F., & Ma, X. (2022) · BMC Complementary Medicine and Therapies · doi:10.1186/s12906-022-03740-9 · Cited by 33 · see citing works
- Authors
- Cao, Y., Xu, R. X., & Liu, Z.
- Affiliations
- The Ohio State University (US)
- University of Science and Technology of China (CN)
- Corresponding author
- Liu, Zhongfa
- Venue
- Journal of Chromatography B
- Publisher
- Elsevier BV
- Published
- 2014-02
- Volume
- 949-950
- Pages
- 70-78
- ISSN
- 1570-0232 (ISSN-L)
- PMC
- PMC4188440
- OpenAlex
- W2089314029
- Cited by
- 84
- References
- 1
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 8 · 2023: 5 · 2022: 11 · 2021: 5 · 2020: 6 · 2019: 12 · 2018: 13 · 2017: 8 · 2016: 6 · 2015: 5 · 2014: 1
- FWCI
- 2.84
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Chromatography B (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (UL1TR001070)
- National Cancer Institute (R21CA159077, R21CA135478)
- National Center for Research Resources (UL1RR025755)
- National Center for Advancing Translational Sciences
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Curcumin's Biomedical Applications
- Physical Sciences › Chemistry › Analytical Chemistry › Analytical Methods in Pharmaceuticals
- Health Sciences › Medicine › Complementary and alternative medicine › Traditional Chinese Medicine Analysis
- Keywords
- curcuminoids, curcumin, demethoxycurcumin, bisdemethoxycurcumin, tetrahydrocurcumin, curcumin metabolites, human plasma quantification, pharmacokinetics, oral bioavailability, LC-MS/MS method validation
- MeSH terms
- Blood Chemical Analysis, Chromatography, High Pressure Liquid, Curcumin, Humans, Sensitivity and Specificity, Reproducibility of Results, Linear Models, Tandem Mass Spectrometry, High-Throughput Screening Assays
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