Development of a liquid-liquid microextraction GC-MS method for simultaneous determination and pharmacokinetic analysis of β- elemene in rat plasma after administration of citronella grass extract / 药学学报

ABSTRACT

We established a simple and sensitive GC-MS method for the determination of β-elemene in rat plasma and measured the pharmacokinetics of citronella grass extract in rats. Plasma samples were pretreated using liquid-liquid microextraction 100 μL of plasma sample (containing naphthalene as the internal standard) was extracted with 50 μL of n-hexane. The determination was performed on DB-5ms column (30 m×0.25 mm, 0.25 μm). The initial column temperature was 60 ℃ and raised to 160 ℃ at a rate of 50 ℃·min-1, maintained for 3 min, and finally increased to 260 ℃ for 3 min. Helium was the carrier gas and the flow rate was 0.15 mL·min-1. The injection volume was 2 μL. EI and selected monitored ions pattern were used for ion scanning with m/z 128 (naphthalene) and m/z 93 (β-elemene). Citronella grass extract was administered to rats by intragastric administration and intravenous administration (containing β-elemene 55 mg·kg-1), and plasma was collected and prepared using an automated blood collection system. The linear range of β-elemene in plasma was 1.0-250 ng·mL-1 (r = 0.997), the limit of quantification was 1.0 ng·mL-1, the accuracy was -4.47% - -0.85%, the extraction recovery was between 56.02%-66.89%, and no obvious matrix effect (94.28%-108.63%) was found. The main pharmacokinetic parameters of β-elemene were AUC0-t (23.56 ± 4.40) ng·mL-1, tmax (1.67 ± 0.58) h, Cmax (7.36 ± 0.69) ng·mL-1, MRT0-t (2.76 ± 0.27) h, t1/2z (2.73 ± 1.36) h, Vz (7.39 ± 3.18) L·kg-1, CLz (1.95 ± 0.51) L·h-1·kg-1, and the absolute bioavailability was about 8.78%. The method is simple, accurate, and sensitive, and is suitable for the pharmacokinetic analysis of β-elemene in citronella grass extract in rats. All animal studies were implemented according to protocols, which were reviewed and approved by the Institutional Animal Care and Use Committee at Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences.