Determination and Pharmacokinetic Study of Pachymic Acid by LC-MS/MS.

Poria cocos is a well-known medicinal plant widely used in China and other East Asian countries owing to its various therapeutic effects. Pachymic acid (PA) is a bioactive lanostrane-type triterpenoid from Poria cocos. In this paper, a method of high-performance liquid chromatographic (LC) coupled with triple quadrupole tandem mass spectrometry (QQQ-MS/MS) was developed and validated to investigate the concentration of PA in rat plasma. Samples were prepared by a liquid-liquid extraction, and chromatographic separation was achieved with a Phenomenex Gemini C18 column (50 mm×2.0 mm i.d.) using a mobile phase consisting of acetonitrile and 0.05% formic acid (85 : 15, v/v) at a flow rate of 0.3 mL/min. The detection was performed on an Applied Bio-Systems API 4000 MS/MS with an electrospray ionization (ESI) inlet in negative multiple reaction monitoring (MRM) mode. Standard curves of samples in plasma were linear (R(2)=0.9948) over the concentration range of 5-500 ng/mL, and acceptable accuracy and precision were achieved. The lower limit of quantification and detection were 5 and 0.5 ng/mL, respectively. The method was used successfully to study the pharmacokinetics of PA in rats for oral administration. The main pharmacokinetic parameters of elimination half-life (t1/2), area under the plasma concentration-time curve from time zero to infinity (AUC0→∞), plasma clearance (CL), and apparent volume of distribution (Vd) for the PA group were 4.96±1.33 h, 1466.9±361.7 ng·h/mL, 6.82±1.73 L/h, and 48.85±9.47 L, respectively. This LC-MS/MS method can be developed further for clinical investigation of PA-containing products.

Study on Pharmacokinetics of Three Preparations from Levistolide A by LC-MS-MS.

A rapid sensitive analytical method was established and validated to investigate levistolide A in rat plasma by liquid chromatography-tandem mass spectrometry operated in the positive ion mode. Levistilide A (LA) and internal standard (IS) andrographolide (AD), mixed with the plasma sample, were separated on a reversed phase Spursil™ C18 5 µm column. The precursor/product transitions (m/z) were 398.5/381.3 for LA and (m/z) 368.0/351.1 for AD. The calibration curve was linear over the range from 5 to 1,250 ng/mL for oral administration and 10-4,000 for intravenous administration with a correlation coefficient (r) ≥0.9993. The lower limit of quantification was 5 ng/mL for LA in plasma. The inter- and intra-day accuracy and precision were less than ±15% of the relative standard deviation. In this study, the developed method is successfully applied to the comparative pharmacokinetic study of LA in rats after oral administration of LA alone, Rhizoma Chuanxiong, and Danggui-Shaoyao-San along with the bioavailability study of LA in rats. Our study shows that low bioavailability (7.5%) is observed after oral administration of LA. Traditional formula compatibility of Danggui-Shaoyao-San could significantly enhance LA bioavailability compared with LA alone and Rhizoma Chuanxiong.