Abstract

A rapid, sensitive and selective high-performance liquid chromatography-tandem mass spectrometric method (HPLC-MS) was developed and validated to determine the 14-(3-methylbenzyl)matrine (3MBM) and 14-(4-methylbenzyl)matrine (4MBM) levels in rat plasma in the present study. The analytes were separated using a C18 column (1.9 μm, 2.1 mm × 100 mm) equipped with a Security Guard C18 column (5 μm, 2.1 mm × 10 mm), followed by detection via triple-quadrupole mass spectrometry using an electrospray ionization (ESI) source. Sample pretreatment involved one-step protein precipitation with isopropanol:ethyl acetate (v/v, 25:75), and pseudoephedrine hydrochloride was used as an internal standard. The method was linear in the concentration range of 5–2000 ng/ml for both compounds. The intra-day and inter-day relative standard deviations (RSDs) were less than 15%, and all relative errors (REs) were within 15%. The proposed method enables the unambiguous identification and quantification of these two compounds in vivo. This study is the first to determine the 3MBM and 4MBM levels in rat plasma after oral administration of these compounds. These results provide a meaningful basis for evaluating the clinical applications of these medicines.

Highlights

  • Matrine (MT, Fig. 1A) is a quinolizidine alkaloid isolated from Sophora alopecuroides, Sophora flavescens or Sophora subprostrata, and it has been used extensively in traditional Chinese medicine for the treatment of viral hepatitis, cancer, and cardiac and skin diseases [1,2,3]

  • Much attention has been paid to the absorption and metabolism of MT and oxymatrine, but few studies on the PKs and pharmacodynamics of these compounds using primarily high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS) have been published [6,7,8,9,10,11,12,13,14]

  • A new high-performance liquid chromatography-tandem mass spectrometric method (HPLC-MS)/MS method was developed and validated for the quantification of 3MBM and 4MBM in rat plasma, which is suitable for the investigation of their PK profiles

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Summary

Introduction

Matrine (MT, Fig. 1A) is a quinolizidine alkaloid isolated from Sophora alopecuroides, Sophora flavescens or Sophora subprostrata, and it has been used extensively in traditional Chinese medicine for the treatment of viral hepatitis, cancer, and cardiac and skin diseases [1,2,3]. To enhance its pharmacological activities, many MT derivatives have been prepared by previous methods [4], and the biological activity of these derivatives was shown to be significantly different. To clarify the difference between the activities of 3MBM and 4MBM, a sensitive and accurate analytical method for the determination of 3MBM and 4MBM levels is required to support pharmacokinetic (PK) studies. To the best of our knowledge, previous studies have examined only the administration of MT or oxymatrine, and no study has reported the pharmacokinetics of 3MBM or 4MBM. A new HPLC-MS/MS method was developed and validated for the quantification of 3MBM and 4MBM in rat plasma, which is suitable for the investigation of their PK profiles

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