[Determination of curcumol in plasma by HPLC-MS/MS method and its pharmacokinetics in Beagle dogs].
To establish a high performance liquid chromatography (HPLC) coupled with tandem mass spectrometry quantitative detection method for the determination of curcumol, the main ingredient of zedoary turmeric oil fat emulsion, and investigate its pharmacokinetics in Beagle dogs, nine healthy Beagle dogs were divided into three groups, and blood samples were collected at scheduled time points after intravenous injection of 7.5, 10 and 12.5 mg x kg(-1) zedoary turmeric oil fat emulsion. The concentrations of curcumol were determined and pharmacokinetics was calculated. A good linearity was obtained from 0.25 to 100 ng x mL(-1) in plasma. The relative recoveries were from 91.33% to 103.17%, and the absolute recoveries were from 31.61% to 37.20%. The intra-day and inter-day variances (RSD) were < 15%. The main pharmacokinetic parameters of curcumol after intravenous injection of 7.5, 10 and 12.5 mg x kg(-1) zedoary turmeric oil fat emulsion were as follows, T1/2 : (2.0 +/- 0.4), (1.7 +/- 0.2) and (2.3 +/- 0.8) h, AUC(0-infinity): (15.1 +/- 2.7), (18.3 +/- 2.0) and (29.5 +/- 4.0) ng x mL(-1) x h; MRT: (0.9 +/- 0.1), (0.8 +/- 0.2) and (0.8 +/- 0.1) h, CL: (21.9 +/- 4.0), (24.9 +/- 6.0) and (18.4 +/- 1.2) L x h(-1) x kg; Vd : (65.4 +/- 26.5), (62.0 +/- 13.4) and (61.2 +/- 19.8) L x kg(-1), respectively. The developed method was rapid, highly sensitive and specific and could be used in curcumol pharmacokinetic studies in vivo. A three-compartment model was best fit to the plasma concentration--time curves obtained in Beagle dogs and the plasma AUC was increased proportionally with doses.
Institute of Clinical Pharmacology, Qilu Hospital of Shandong University, Jinan 250012, China.
Rui
R
Zhang
Ben-Jie
BJ
Wang
Heng-Li
HL
Zhao
Xiao-Li
XL
Li
Chun-Min
CM
Wei
Rui-Chen
RC
Guo
D000818:Animals; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D030024:Curcuma / Q000737:chemistry; D004285:Dogs; D004365:Drugs, Chinese Herbal / Q000302:isolation & purification / Q000493:pharmacokinetics; D008297:Male; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification; D010938:Plant Oils / Q000737:chemistry / Q000302:isolation & purification; D010946:Plants, Medicinal / Q000737:chemistry; D011897:Random Allocation; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D012717:Sesquiterpenes / Q000097:blood* / Q000302:isolation & purification / Q000493:pharmacokinetics*; D053719:Tandem Mass Spectrometry / Q000379:methods
D004365:Drugs, Chinese Herbal; D010936:Plant Extracts; D010938:Plant Oils; D012717:Sesquiterpenes; C012596:turmeric extract; C022801:curcumol