PMID- 21856253 OWN - NLM STAT- MEDLINE DCOM- 20111114 LR - 20220405 IS - 1873-376X (Electronic) IS - 1570-0232 (Linking) VI - 879 IP - 26 DP - 2011 Sep 15 TI - 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. PG - 2751-8 LID - 10.1016/j.jchromb.2011.07.042 [doi] AB - 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. CI - Copyright (c) 2011 Elsevier B.V. All rights reserved. FAU - Li, Rui AU - Li R AD - State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Beijing 100191, China. FAU - Qiao, Xue AU - Qiao X FAU - Li, Qingyan AU - Li Q FAU - He, Rong AU - He R FAU - Ye, Min AU - Ye M FAU - Xiang, Cheng AU - Xiang C FAU - Lin, Xionghao AU - Lin X FAU - Guo, Dean AU - Guo D LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20110806 PL - Netherlands TA - J Chromatogr B Analyt Technol Biomed Life Sci JT - Journal of chromatography. B, Analytical technologies in the biomedical and life sciences JID - 101139554 RN - 0 (Biphenyl Compounds) RN - 0 (Diarylheptanoids) RN - 0 (Lignans) RN - 0 (Lipids) RN - 11513CCO0N (honokiol) RN - 2EFO1BP34R (bisdemethoxycurcumin) RN - IT942ZTH98 (Curcumin) RN - W2F8059T80 (demethoxycurcumin) SB - IM MH - Animals MH - Area Under Curve MH - Biphenyl Compounds/chemistry MH - Chromatography, Liquid/*methods MH - Curcumin/administration & dosage/*analogs & derivatives/metabolism/pharmacokinetics MH - Diarylheptanoids MH - Drug Delivery Systems MH - Drug Stability MH - Lignans/chemistry MH - Linear Models MH - Lipids MH - Male MH - Mice MH - Mice, Inbred ICR MH - Nanoparticles/*administration & dosage/chemistry MH - Neoplasm Transplantation MH - Neoplasms/chemistry/*metabolism MH - Reproducibility of Results MH - Tandem Mass Spectrometry/*methods EDAT- 2011/08/23 06:00 MHDA- 2011/11/15 06:00 CRDT- 2011/08/23 06:00 PHST- 2011/05/16 00:00 [received] PHST- 2011/07/23 00:00 [revised] PHST- 2011/07/31 00:00 [accepted] PHST- 2011/08/23 06:00 [entrez] PHST- 2011/08/23 06:00 [pubmed] PHST- 2011/11/15 06:00 [medline] AID - S1570-0232(11)00510-1 [pii] AID - 10.1016/j.jchromb.2011.07.042 [doi] PST - ppublish SO - J Chromatogr B Analyt Technol Biomed Life Sci. 2011 Sep 15;879(26):2751-8. doi: 10.1016/j.jchromb.2011.07.042. Epub 2011 Aug 6.