[Pharmacokinetics of triptolide in Beagle dogs].
The aim of this paper is to develop and validate a rapid and sensitive LC-APCI/MS method for the determination of triptolide (TP) in plasma and to study the pharmacokinetic properties of TP in Beagle dogs. Sample preparation consisted of liquid-liquid extraction of interests. with ethyl acetate from dog plasma. The analytes and internal standard prednisolone were well separated on a Zorbax Extend-C18 analytical column. Plasma TP was detected by selected-ion monitoring (SIM) of LC-APCI/MS as its deprotonated molecular ions [M - H] - at m/z 358.9. Pharmacokinetic studies were undertaken in dogs following an iv dose of 0.05 mg x kg(-1) of TP or an ig dose of 0.05, 0.08, 0.1 mg x kg(-1), separately. The pharmacokinetic parameters were calculated by DAS software. Calibration curves were linear over the concentration range of 1 - 200 ng x mL(-1) of TP with the within- and between-batch precisions less than 10%. The within and between-batch accuracy was 95.0% to 105.0%. Recovery of LC-MS method for TP in plasma was over 75%. The T1/2beta was (2.5 +/- 0.8) h after intravenous administration of TP at the dose of 0.05 mg x kg(-1). There were no significant differences in T(max), T1/2 alpha and T1/2 beta among the three ig dosage groups. AUC and C(max) increased proportionally with doses. The absolute bioavailability of TP after ig administration of 0.05 mg x kg(-1) was (75 +/- 17)%. The LC-MS method for determination of triptolide in dog plasma was sensitive and rapid. It was showed that the elimination of triptolide was rapid. The absolute bioavailability of triptolide given orally was high.
Shao
Feng
F
Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, China.
Wang
Guang-Ji
GJ
Sun
Jian-Guo
JG
Xie
Hai-Tang
HT
Zhang
Rong
R
Zhu
Xiao-Yan
XY
D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D004224:Diterpenes / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004852:Epoxy Compounds / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D005260:Female; D007275:Injections, Intravenous; D008297:Male; D013058:Mass Spectrometry; D010616:Phenanthrenes / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D010946:Plants, Medicinal / Q000737:chemistry; D011897:Random Allocation; D029757:Tripterygium / Q000737:chemistry*
D004224:Diterpenes; D004852:Epoxy Compounds; D010616:Phenanthrenes; C001899:triptolide