A GC-SIM-MS Method for the Determination of Butylidenephthalide in Rat Plasma and Tissue: Application to the Pharmacokinetic and Tissue Distribution Study

Abstract

Butylidenephthalide is one of the major active components isolated from Rhizoma Chuanxiong. This paper describes a simple, rapid, specific and sensitive method for the quantification of butylidenephthalide in rat plasma and tissue distribution using a liquid-liquid extraction procedure followed by capillary gas chromatography-selected ion monitoring mode-mass spectrometry (GC-SIM-MS) analysis. The calibration curves were linear over the concentration ranging from 0.02-10.0 mg=mL (r > 0.99) for plasma samples and 0.18-7.25 mg=g (r > 0.99) for the tissue samples. The limit of quantification (LOQ) was 1.0 ng=mL or 1.0 ng=g (ten times signal=noise ratio). Within-and between-day precisions expressed as the relative standard deviation (RSD) for the method were 2.39-2.98% and 2.97-4.26%, respectively. The methods of recovery for all samples were greater than 80% at the low, medium, and high concentrations. The method has been successfully applied to a pharmacokinetics study in rats after an oral administration of Butylidenephthalide with a dose of 20.0 mg=kg. The main pharmacokinetic parameters obtained were T max ¼ (0.22 AE 0.06) h, C max ¼ (3 AE 1) mg=mL, AUC ¼ (32 AE 6) h . mg=mL, and K a ¼ (8.5 AE 0.8)=h. The results showed that the butylidenephthalide was easily absorbed. The concentrations of butylidenephthalide in rat kidney, lung, heart, and cerebellum were higher than those in other organs. To determine free fraction in serum, samples were filtered using ultrafiltration membranes with a molecular weight cut-off of 10,000 Da and extracted using liquid-liquid extraction. The extracts were evaporated and analyzed by GC-MS. The protein binding in rat plasma, human plasma, and human serum albumin were 83 AE 4%, 94 AE 3%, and 89 AE 3%, respectively.

A novel GC–MS method for determination of chrysophanol in rat plasma and tissues: Application to the pharmacokinetics, tissue distribution and plasma protein binding studies

“…The elimination rate constant (Ke) was calculated by linear egression of the terminal semi-log plot of plasma concentration versus time, and t 1/2 was calculated as 0.693/Ke. The tissue distributions of chrysophanol in rat's tissue were evaluated by measuring the concentrations of chrysophanol at 1.2 h after the oral administration (at about 30 min after the time of T max , which was indicate a wide tissue distribution of drug in rat after the administration) [14,15,19]. All data were expressed as means ± standard deviation.…”

“…In addition, GC-MS is an important analytical tool for MS detection performed in selected ion monitoring (SIM) mode by which the sensitivity can be increased. The applications of GC-MS in the study the pharmacokinetics and tissue distribution of active compounds in herbs have been well investigated by our groups [13][14][15]. However, there are still no reports for the determination of chrysophanol by GC-MS.…”