Simultaneous determination of three triterpenes in rat plasma by LC–MS/MS and its application to a pharmacokinetic study of Rhizoma Alismatis extract.

We have developed a sensitive and specific LC–MS/MS method for the simultaneous determination of alisol A ( A ), alisol A 23-acetate ( A23 ) and alisol A 24-acetate ( A24 ), the major active components in Rhizoma Alismatis extract ( RAE ), in rat plasma. In brief, plasma samples were extracted by methyl tert -butyl ether and chromatographically separated by using a C 18 column. A tandem mass spectrometric detection with an electrospray ionization (ESI) interface was conducted via multiple reaction monitoring (MRM) under positive ionization mode. This method was validated for specificity, linearity, accuracy (within ±15.4%), intra- and inter-day precision (CV < 11.4%) over the concentration range of 25–5000 ng/mL for A, and 5–1000 ng/mL for both A23 and A24 . The significantly lower detection limit was determined as 25 ng/mL for A , 5 ng/mL for A23 and A24 . This validated method of ours was then used to study the pharmacokinetics of RAE in rat. The elimination half-lives ( t 1/2 ) of A , A23 and A24 was determined as 0.75, 0.83 and 0.82 h respectively after intravenous injection, and the oral absolute bioavailability of A , A23 and A24 was 43.1 ± 18.1%, 6.3 ± 1.5% and 7.9 ± 1.2%. This new determination method of us for alisols is proven to very useful to study the pharmacological activities of RAE in future. [ABSTRACT FROM AUTHOR]