Determination and pharmacokinetic study of oxymatrine and its metabolite matrine in human plasma by liquid chromatography tandem mass spectrometry.
There is little information about the pharmacokinetics of oxymatrine (OMT) and its metabolite matrine (MT) after i.v. administration of OMT in human. Therefore a specific and sensitive liquid chromatography tandem mass spectrometry (LC-MS/MS) method was established for the determination and pharmacokinetic study of OMT and its metabolite MT in human plasma after i.v. infusion administration of 600 mg of OMT in 100 ml of 5% glucose injection in 0.5 h. The analysis was carried out on a Lichrospher-CN column (250 mmx4.6 mm, i.d., 5 microm, Merck) with mobile phase of methanol-ammonium acetate (20 mmol/l; 85:15, v/v) pumped at a flow rate of 1.0 ml/min. The tandem mass detection was made with electrospray ionization in positive ion selected reaction monitoring mode, with argon collision-induced dissociation ion transitions m/z 265.2 to m/z 265.2 for OMT at 25 eV, m/z 249.2 to m/z 249.2 for MT at 25 eV and m/z 340.2 to m/z 324.0 at 35 eV for the internal standard (papaverine), respectively. The assay was validated to be accurate and precise for the analysis in the concentration range of 1.0-40,000 ng/ml for both OMT and MT with the LOD being 0.5 and 0.2 ng/ml, respectively, when 0.25 ml of human plasma sample was processed with papaverine as internal standard. The pharmacokinetic study was made with 10 healthy male Chinese subjects. The plasma concentration time profiles of OMT and MT obtained were best fitted with two-compartment and one-compartment models, respectively. The main pharmacokinetic parameters found for OMT and MT after i.v. infusion were as follows: Cmax (20,519+/-7581) and (247+/-45) ng/ml, Tmax (0.5+/-0.1) and (5.6+/-1.7) h, AUC0-t (20,360+/-5205) and (3817+/-610) ng h/ml, AUC0-infinity (20,436+/-5188) and (3841+/-615) ng h/ml, t1/2 (2.17+/-0.49) and (9.43+/-0.62) h, respectively. The CL/F and Vd/F of OMT were (43.8+/-10.8) l h-1 and (70.1+/-26.6) l, respectively. Therefore only a small amount of OMT was reduced to MT following i.v. administration of OMT judged by the AUCs.
Wu
Xiao-luan
XL
Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing 210009, PR China.
Hang
Tai-jun
TJ
Shen
Jian-ping
JP
Zhang
Yin-di
YD
D000470:Alkaloids / Q000097:blood* / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002853:Chromatography, Liquid / Q000379:methods*; D006207:Half-Life; D006801:Humans; D008297:Male; D011807:Quinolizines / Q000097:blood*; D012015:Reference Standards; D015203:Reproducibility of Results; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D000093842:Matrines
D000470:Alkaloids; D011807:Quinolizines; C037573:oxymatrine; D000093842:Matrines