RESUMO
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.
Assuntos
Anticarcinógenos/farmacocinética , Espectrometria de Massas/métodos , Sapogeninas/farmacocinética , Administração Oral , Animais , Anticarcinógenos/administração & dosagem , Anticarcinógenos/química , Área Sob a Curva , Pressão Atmosférica , Disponibilidade Biológica , Calibragem , Cromatografia Líquida de Alta Pressão/métodos , Guias como Assunto , Meia-Vida , Injeções Intravenosas , Masculino , Taxa de Depuração Metabólica , Estrutura Molecular , Controle de Qualidade , Ratos , Ratos Sprague-Dawley , Padrões de Referência , Reprodutibilidade dos Testes , Sapogeninas/administração & dosagem , Sapogeninas/química , Sensibilidade e Especificidade , Espectrometria de Massas por Ionização por Electrospray/métodosRESUMO
OBJECTIVE: To establish a method for HPLC fingerprint determination of the triterpene acids in Poria cocos. METHOD: RP-HPLC, linear gradient elution and LC/MS, etc. were used to optimize the fingerprint determination method, and identify the main peaks in the HPLC fingerprint. RESULT: A preferable method for HPLC fingerprint determination of the triterpene acids in P. cocos was established, and 9 peaks in the HPLC fingerprint were identified. CONCLUSION: A general acquaintance of the triterpene acids in P. cocos can be obtained by using the preferable HPLC fingerprint determination method, which is useful for quality evaluation of the crud drug of P. cocos.