Gas chromatography-mass spectrometry determination of matrine in human plasma

doi:10.1016/j.jchromb.2004.05.010

Journal of Chromatography B

Volume 808, Issue 2, 5 September 2004, Pages 209-214

https://doi.org/10.1016/j.jchromb.2004.05.010 Get rights and content

Abstract

A method was developed for the quantification of matrine in human plasma using a liquid–liquid extraction procedure followed by gas-chromatography-mass spectrometry (GC/MS) analysis. Deuterated matrine, an internal standard of the analysis, was spiked into the plasma samples before extraction. Linear detection responses were obtained for matrine concentrations ranging from 10 to 500 ng/ml. The intra-day and inter-day precision ranged from 0.4 to 4.0% and 1.0–3.5%, respectively. The intra-day accuracy was between −7.3 and 4.5%. The limit of quantification for matrine was 23 ng/ml. The extraction efficiency averaged about 38%. The validated GC/MS method will be used to quantify matrine in human plasma samples collected in a clinical trial study.

Introduction

The roots of Sophora tonkinensis, S. alopecuroides, and S. flavescens have a wide range of pharmacological and toxicological activities [1]. Therefore, these roots have been used as traditional herbal medicine in China, Japan, and Korea to treat diseases such as cancer, viral hepatitis, cardiac arrhythmia, asthma, and skin problems [2].

About 2% of the S. flavescens roots (dry weight) are composed of alkaloids with matrine (Fig. 1a) and oxymatrine as the major components [3]. Several minor alkaloids including sophoranol, sophocarpine, and sophordine also have been found in the S. flavescens roots [4].

Although the S. flavescens roots have been used for disease treatment, very little is known of the absorption, distribution, metabolism and excretion of matrine and oxymatrine in humans. After oral administration to human or animals, oxymatrine was converted by the gastrointestinal tract and liver to matrine [5]. In the only pharmacokinetic study reported for humans [6], a large dose of pure matrine (6 mg/kg) was infused intravenously to the experimental subjects and blood samples were withdrawn at specific time points post-dosing. A HPLC/UV method was used to determine matrine concentrations in the blood, which ranged from 1 to 6 μg/ml [6]. However, the HPLC/UV method probably is not sensitive enough for detecting matrine in the plasma of humans receiving an oral dose of the S. flavescens roots due to the small amount of matrine in S. flavescens roots and the low bioavailability of matrine in humans. The concentrations of matrine in the blood of humans after ingestion of S. flavescens roots is presently unknown but they are expected to be much lower than 1 μg/ml.

The purposes of the present work were to develop and validate a sensitive GC/MS method, which could be used to detect matrine in the plasma of human at low ng/ml concentrations. The novel GC/MS method used deuterated matrine as the internal standard and liquid–liquid extraction for sample preparation.

Section snippets

Reagents and chemicals

Chemicals were purchased from the following sources: matrine from the National Institute for the Control of Pharmaceutical and Biological Products (Beijing, China). Toluene and hydrochloric acid from Anachemia Co. (Montreal, Que., Canada). Petroleum ether and sodium sulfate from BDH (Toronto, Ont., Canada). Sodium hydroxide solution (1 M) was from VWR (West Chester, PA, USA). Butanol from Caledon (Georgetown, Ont., Canada). Sodium deuteroxide (40%, in water), deuterium oxide and deuterated

Results and discussion

The present work describes the development and validation of a GC/MS method, which uses deuterated matrine as the internal standard to determine matrine concentration in human plasma. Although both hydrogens at position 14 of the matrine molecule (see Fig. 1a) could be activated with respect to deuterium exchange under basic conditions [8], less than 30% isotopic enrichment was achieved using sodium deuteroxide synthesized in situ from deuterium oxide and sodium at our laboratory. However, when

Acknowledgements

This work was supported by research grants from the US National Cancer Institute and Natural Science and Engineering Research Council of Canada.

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