A Simple Gas Chromatographic Method for the Simultaneous Determination and Pharmacokinetic Study of Tetramethylpyrazine Phosphate and Borneol in Mouse Plasma and Brain Tissue After Oral Administration of the Fufang Tetramethylpyrazine Phosphate Tablets

Journal of Chromatographic Science, May 2008

A rapid, sensitive, and simple gas chromatographic method with flame ionization detection is developed for the simultaneous determination of tetramethylpyrazine phosphate (TMPP) and borneol in mouse plasma and brain tissue. Sample preparations are carried out by deproteinization with an internal standard solution in methanol. The analytes and internal standard (dimethyl sulfoxide) are well-separated on an HP-5 MS capillary column. The analytical curves are linear over a wide concentration range of 0.02–40 μg/mL for both TMPP and borneol in plasma and brain tissue, with the intra- and inter-day precision (the relative standard deviation values) at less than 15%. TMPP and borneol are both stable under different conditions. The method described is successfully applied to the pharmacokinetic study of mouse plasma and brain tissue after oral administration of the Fufang TMPP and TMPP tablets to mice.

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A Simple Gas Chromatographic Method for the Simultaneous Determination and Pharmacokinetic Study of Tetramethylpyrazine Phosphate and Borneol in Mouse Plasma and Brain Tissue After Oral Administration of the Fufang Tetramethylpyrazine Phosphate Tablets

Journal of Chromatographic Science A Simple Gas Chromatographic Method for the Simultaneous Determination and Pharmacokinetic Study of Tetramethylpyrazine Phosphate and Borneol in Mouse Plasma and Brain Tissue After Oral Administration of the Fufang Tetramethylpyrazine Phosphate Tablets Xiao Yan-yu 0 Ping Qi-neng 0 Chen Zhi-peng 0 0 Department of Pharmacy, China Pharmaceutical University , 210009 Nanjing , China A rapid, sensitive, and simple gas chromatographic method with flame ionization detection is developed for the simultaneous determination of tetramethylpyrazine phosphate (TMPP) and borneol in mouse plasma and brain tissue. Sample preparations are carried out by deproteinization with an internal standard solution in methanol. The analytes and internal standard (dimethyl sulfoxide) are well-separated on an HP-5 MS capillary column. The analytical curves are linear over a wide concentration range of 0.02-40 μg/mL for both TMPP and borneol in plasma and brain tissue, with the intra- and inter-day precision (the relative standard deviation values) at less than 15%. TMPP and borneol are both stable under different conditions. The method described is successfully applied to the pharmacokinetic study of mouse plasma and brain tissue after oral administration of the Fufang TMPP and TMPP tablets to mice. Introduction Tetramethylpyrazine phosphate (TMPP) (Figure 1A) has been widely used in China for the treatment of cardiovascular and cerebrovascular disorders ( 1–3 ). It has been found to block calcium channels, reduce the bioactivity of platelets and platelet aggregation, inhibit free radicals, increase cerebral blood flow ( 4–6 ), and improve blood viscosity ( 7 ). However, TMPP possesses a low oral bioavailability (10–30%) after oral administration, due to hepatic first pass metabolism ( 8 ). Borneol (Figure 1B and 1C), a monoterpenoid alcohol, is isolated from Fructus amoni. Recently, it has been reported that borneol can increase the oral bioavailability of TMPP and enhance its distribution in brain tissue. To increase oral bioavailability of TMPP and to enhance its distribution in brain tissue, the Fufang TMPP tablets containing TMPP and borneol were developed for the treatment of cerebral thrombosis. Therefore, it was necessary to establish a sensitive and simple method to simultaneously determinate TMPP and borneol in biological fluids. To date, several analytical methods have been developed for the determination of tetramethylpyrazine (TMP) and borneol in biological fluids. Peng et al. ( 9 ) determined the concentrations of TMP and its metabolite in dog plasma using a liquid chromatographic–mass spectrometric (LC–MS) method. Tung-Hu et al. ( 10 ) researched the pharmacokinetics of TMP in rat blood and brain using microdialysis. Liang et al. ( 11–12 ) measured the pharmacokinetics of TMP in rat blood and regional brain tissue by high-performance LC with UV detection, and also studied the pharmacokinetics of borneol in rat blood and brain tissue by gas chromatography (GC). Guo et al. (13) studied the simultaneous determination of TMP and bornoel in human plasma, administrated with Suxiao Jiuxin Wan. But most of those methods require complicated sample preparation procedures involving basification of the plasma sample, extraction, acidification, preconcentration, and reconstitution of the analytes. These procedures are rather time-consuming and more complex than the procedure described in this paper. With this method, samples using dimethyl sulfoxide as an internal standard could be applied to GC with flame ionization detection (FID) with simple deproteinization and without multiple pretreatment steps. The present method was also successfully applied to the pharmacokinetic study of mouse plasma and brain tissue after oral administration of the Fufang TMPP tablets and TMPP tablets to mice. Experimental Materials Tetramethylpyrazine phosphate (TMPP, 99.8% purity) was purchased from Beijing Yanjing Pharmaceutical Factory (Beijing, China). Borneol (99.4% purity) and dimethyl sulfoxide (internal standard, I.S.) was obtained from Shanghai Chemical Reagent Co. (Shanghai, China). The other chemical reagents were of analytical grade or better. The reference formulation consisted of TMPP tablets purchased from Beijing Yanjing Pharmaceutical Factory (Beijing, China). Each tablet contains 50 mg of TMPP. The Fufang TMPP tablets were prepared in our laboratory. Each tablet contains 50 mg of TMPP and 40 mg of borneol. Instrument and chromatographic conditions The GC–FID system consisted of an HP 4890 gas chromatographic system, an FID (Agilent 4890, Palo Alto, CA), and Agilent Chemstation software for data analysis. Separation of TMPP, borneol, and I.S. from endogenous substances was performed on an HP-5 MS capillary column (30.0 m × 250 μm, A B Downloaded fr3o9m6https://academic.oup.com/chromsci/article-abstract/46/5/395/372579 by guest on 23 May 2018 0.25 μm). Nitrogen, at a flow rate o (...truncated)


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Xiao, Yan-yu, Ping, Qi-neng, Chen, Zhi-peng. A Simple Gas Chromatographic Method for the Simultaneous Determination and Pharmacokinetic Study of Tetramethylpyrazine Phosphate and Borneol in Mouse Plasma and Brain Tissue After Oral Administration of the Fufang Tetramethylpyrazine Phosphate Tablets, Journal of Chromatographic Science, 2008, pp. 395-400, Volume 46, Issue 5, DOI: 10.1093/chromsci/46.5.395