A high-throughput quantification method of curcuminoids and curcumin metabolites in human plasma via high-performance liquid chromatography/tandem mass spectrometry

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 2-1000 ng/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). (C) 2014 Elsevier B.V. All rights reserved.