Abstract

Sodium Danshensu (sodium d-(+)-β-(3,4-dihydroxyphenyl) lactate), one of the water-soluble ingredients in Salvia miltiorrhiza, exhibits potent relaxation of the coronary artery and anticoagulation effection. A high-throughput, rapid, and sensitive method combining liquid chromatography with electrospray ionization tandem mass spectrometry to determine the sodium danshensu in beagle dog plasma was developed and validated, using gallic acid as an internal standard (IS). Acidified plasma samples were extracted using 96-well liquid-liquid extraction, and were eluted on a CNW Athena C18 column (3 μm, 2.1 × 100 mm) by using a gradient mobile phase system of methanol and water (containing 0.2% formic acid). The mass spectrometric detection was achieved using negative ion electrospray ionization mode and monitoring the precursor→production combinations of m/z 197→135 for sodium danshensu and 169→125 for IS, in multiple reaction monitoring modes. Good linearity was achieved, and the linear range was 10–1000 ng/mL (R2 > 0.996) with a quantification limit of 10 ng/mL for sodium danshensu in beagle dog plasma. The intra- and inter-day precision (RSD) ranged from 2.1% to 9.0%. The accuracy (RE) was between −8.6% and 5.7% at all quality control levels. The validated method was successfully applied to the pharmacokinetics study of sodium danshensu in beagle dog plasma after intravenous injection and oral administration of sodium danshensu.

Highlights

  • Sodium danshensu (sodium D-(+)-β-(3,4-dihydroxyphenyl) lactate) is a sodium salt of danshensu extracted from Danshen (Figure 1)

  • The result demonstrated that the protein precipitation using methanol or acetonitrile as the extraction solvent resulted in low extraction recovery during the procedure

  • The linearity is good over the linear range of 10–1000 ng/mL with the lower limit of quantitation of 10 ng/mL for investigating the sodium danshensu in beagle dog plasma

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Summary

Introduction

Sodium danshensu (sodium D-(+)-β-(3,4-dihydroxyphenyl) lactate) is a sodium salt of danshensu extracted from Danshen (Figure 1). According to especially in cases of hepatitis, and cerebrovascular and cardiovascular diseases [1], such as cardiodynia, the study of phytochemistry, the main bioactive constituents in the roots of Danshen can be classified myocardial infarction [2], intimal hyperplasia, and attenuated restenosis [3]. According to the study phytochemistry, the main bioactive constituents the compounds roots of Danshen can lipophilic be classified into into of two broad categories: the hydrophilic phenolicinacid and the tanshinone two broad categories: the hydrophilic phenolic acid compounds the constituents lipophilic tanshinone compounds [4,5] Among these constituents, danshensu is one of theand major of hydrophilic compounds [4,5]. Sodium danshensu as a candidate compound compound has attracted considerable attention, it is necessary to study the pharmacodynamics, has attracted considerable attention, and it and is necessary to study the pharmacodynamics, pharmacokinetics, and safety of sodium danshensu

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