title: Metabolic and pharmacokinetic studies of curcumin, demethoxycurcumin and bisdemethoxycurcumin in mice tumor after intragastric administration of nanoparticle formulations by liquid chromatography coupled with tandem mass spectrometry.
abstract: This paper aims to investigate the metabolism and pharmacokinetics of curcumin, demethoxycurcumin and bisdemethoxycurcumin in mice tumor. To improve water solubility, nanoparticle formulations were prepared as curcuminoids-loaded solid lipid nanoparticles (curcuminoids-SLNs) and curcumin-loaded solid lipid nanoparticles (curcumin-SLNs). After intragastric administration to tumor-bearing ICR mice, the plasma and tumor samples were analyzed by liquid chromatography with ion trap mass spectrometry. We discovered that curcuminoids were mainly present as glucuronides in plasma, whereas in free form in tumor tissue. A validated LC/MS/MS method was established to determine the three free curcuminoids in tumor homogenate. Samples were separated on a Zorbax SB-C(18) column, eluted with acetonitrile-water (containing 0.1% formic acid), and detected by TSQ Quantum triple quadrupole mass spectrometer in selected reaction monitoring mode. The method showed good linearity (r(2)=0.997-0.999) over wide dynamic ranges (2-6000 ng/mL). Variations within- and between-batch never exceeded 11.2% and 13.4%, respectively. The extraction recovery rates ranged from 78.3% to 87.7%. The pharmacokinetics of curcuminoids in mice tumor fit two-compartment model and first order elimination. For curcumin-SLNs group, the dosing of 250 mg/kg of curcumin resulted in AUC((0-48 h)) of 2285 ngh/mL and C(max) of 209 ng/mL. For curcuminoids-SLNs group, the dosing equivalent to 138 mg/kg of curcumin resulted in higher tumor concentrations (AUC=2811 ngh/mL, C(max)=285 ng/mL). It appeared that co-existing curcuminoids improved the bioavailability of curcumin.
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Beijing 100191, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Li
authors.forename: Xue
authors.initials: X
authors.lastname: Qiao
authors.forename: Qingyan
authors.initials: Q
authors.lastname: Li
authors.forename: Rong
authors.initials: R
authors.lastname: He
authors.forename: Min
authors.initials: M
authors.lastname: Ye
authors.forename: Cheng
authors.initials: C
authors.lastname: Xiang
authors.forename: Xionghao
authors.initials: X
authors.lastname: Lin
authors.forename: Dean
authors.initials: D
authors.lastname: Guo
mesh_terms: D000818:Animals; D019540:Area Under Curve; D001713:Biphenyl Compounds / Q000737:chemistry; D002853:Chromatography, Liquid / Q000379:methods*; D003474:Curcumin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics; D036381:Diarylheptanoids; D016503:Drug Delivery Systems; D004355:Drug Stability; D017705:Lignans / Q000737:chemistry; D016014:Linear Models; D008055:Lipids; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000737:chemistry / Q000378:metabolism*; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry / Q000379:methods*; D000498:Allyl Compounds; D010636:Phenols
chemical_list: D001713:Biphenyl Compounds; D003474:Curcumin; D036381:Diarylheptanoids; D017705:Lignans; D008055:Lipids; C005499:honokiol; D000498:Allyl Compounds; D010636:Phenols; C034786:bisdemethoxycurcumin; C050229:demethoxycurcumin