Sensitive determination of 20(S)-protopanaxadiol in rat plasma using HPLC-APCI-MS: application of pharmacokinetic study in rats.
20(S)-Protopanaxadiol (PPD), the main metabolite of protopanoxadiol type ginsenosides (e.g. Rg3 and Rh2), is a very promising anti-cancer drug candidate. To evaluate the pharmacokinetic property of PPD, we reported a reliable, sensitive and simple method utilizing liquid chromatography (HPLC)-atmospheric pressure chemical ionization-mass spectrometry (APCI-MS) to determine PPD. PPD and the internal standard, panoxadiol (PD) were extracted from plasma with acetic ether, separated on a C18 reverse column, and then analyzed by APCI-MS. Targeting fragment ion at m/z 425 for both PPD and PD was monitored in selected-ion monitoring (SIM) mode. PPD can be quantitatively determined at the concentration as low as 1 ng/mL using 200 microL plasma. And the sensitive method showed excellent linearity over a range from 1 to 1000 ng/mL, high recovery, accuracy and precision at the concentrations of 2.5, 100.0 and 1000.0 ng/mL, respectively. The method was successfully applied to pharmacokinetic study of PPD in rats. Pharmacokinetic parameters were calculated and absolute bioavailability of PPD was 36.8+/-12.4%, at least ten times higher than that of Rg3 and Rh2, indicating its good absorption in gastrointestinal tract. It was further suggested that PPD be a promising anti-cancer candidate and probably responsible for the observed pharmacological activity of Rg3 and Rh2.
Ren
Hong-Can
HC
Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210038, PR China.
Sun
Jian-Guo
JG
Wang
Guang-Ji
GJ
A
Ji-Ye
JY
Xie
Hai-Tang
HT
Zha
Wei-Bin
WB
Yan
Bei
B
Sun
Fen-Zhi
FZ
Hao
Hai-Ping
HP
Gu
Sheng-Hua
SH
Sheng
Long-Sheng
LS
Shao
Feng
F
Shi
Jian
J
Zhou
Fang
F
D000284:Administration, Oral; D000818:Animals; D016588:Anticarcinogenic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001274:Atmospheric Pressure; D001682:Biological Availability; D002138:Calibration; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D017408:Guidelines as Topic; D006207:Half-Life; D007275:Injections, Intravenous; D008297:Male; D013058:Mass Spectrometry / Q000379:methods*; D008657:Metabolic Clearance Rate; D015394:Molecular Structure; D011786:Quality Control; D051381:Rats; D017207:Rats, Sprague-Dawley; D012015:Reference Standards; D015203:Reproducibility of Results; D012502:Sapogenins / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods
D016588:Anticarcinogenic Agents; D012502:Sapogenins; C062916:protopanaxadiol