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Relative bioavailability of gastrodin and parishin from extract and powder of Gastrodiae rhizoma in rat

https://doi.org/10.1016/j.jpba.2014.08.017Get rights and content

Highlights

  • An UHPLC-MS/MS method was developed to assay gastrodin and parishin in rat plasma.

  • We applied the method for pharmacokinetics study on the two analytes.

  • The powder maximizes the exposure to gastrodin and parishin at low dosage.

  • The extract maximizes the exposure to the two analytes at medium and high dosages.

  • Powder cannot be regarded as the best medicinal form just due to its preciousness.

Abstract

A rapid, sensitive and reliable UHPLC-ESI-MS/MS method was developed for simultaneous determination of gastrodin and parishin in rat plasma. The LLOQ of the two analytes were 1.00 × 10−1 and 8.30 × 10−5 μg/mL, respectively. The intra-day and inter-day precision were all less than 10% of the relative standard deviation (RSD), whilst the accuracy were all within ±15% of the relative error (RE). The proposed method was successfully applied for pharmacokinetics study on the two analytes in rats after oral administration of Gastrodiae rhizoma (GR) extract and powder at low, medium and high dosages. Blood samples were collected from the suborbital vein at predetermined time points and were precipitated using methanol. Chromatographic separations were carried out on a Kinetex XB-C18 column (2.1 mm × 150 mm, 1.7 μm) with a gradient mobile phase of acetonitrile-water with 0.1% formic acid as a modifier. The pharmacokinetic parameters of the two analytes in rats were obtained and the relative bioavailability of gastrodin and parishin in two formulations were calculated. The results indicated that higher bioavailability was obtained when low dosage of GR powder was used, whereas, higher bioavailability values were obtained when medium and high dosages of GR extract were used.

Graphical abstract

The pharmacokinetic parameters of gastrodin and parishin in rats were obtained and the relative bio-availabilities of the two analytes in two dosage forms were calculated. The results indicated that GR powder at low dosage gained higher bio-availability, however, GR extract gained higher bio-availability at medium and high dosages.

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Introduction

Gastrodiae rhizoma (GR), Tianma in Chinese, is the dried rhizomes of Gastrodia elata Blume. (Orchidaceae) and is officially listed in Chinese Pharmacopeia (CP) (Edition 2010) [1] as one of the commonly used Chinese medicines for the treatment of febrile convulsion, epileptoid convulsion, tetanus, headache or dizziness and paralysis or numbness of the limbs. Modern pharmacological studies indicated that aqueous extract of GR had anxiolytic-like effects [2] and relatively good favorable effect on prevention and/or treatment of ovariectomy (OVX)-induced osteoporosis [3]. Fifty percent alcohol extract of GR was testified to have a protective effect against neuronal damage in KA-treated rats by reducing nNOS, microglia activation and apoptosis [4] and have anticonvulsive and free radical scavenging activities [5]. Ether fraction of methanol extract of GR was also investigated and the anticonvulsive effect and putative neuroprotective effect against excitotoxicity were reported [6].

Phytochemical studies on GR have revealed the presence of gastrol, phenolic compounds [7], polysaccharides [8], amino acids, nucleosides [9], adenosines [10], vanillyl alcohol [11], gastrodin [10], [12], [13] and parishins [13], [14]. Gastrodin is one of the earliest compounds found in GR and is specified as a marker for quality assessment on the herb in CP (edition 2010). The compound was reported to decrease immune reactivities of gamma-aminobutyric acid shunt enzymes in the hippocampus of seizure sensitive gerbils [15], to play protective action against liver injury induced by CCl4 in mice [16] and to cure vascular headache with effective rate at 91%. The compound is available in oral formulations and has been reported to be used intravenously and intramuscularly in clinical trials. Parishin, a main highly polar compound from aqueous extract of GR, significantly enhanced the ADCC reaction [17]. The two analytes have been assayed for quality assessment on GR and its related formulas in different analytical approaches [18], [19].

GR extract has been manufactured by many Chinese pharmaceutical or biotechnological companies used clinically as therapeutic medicine. However, due to the valuableness of the herb, more and more pharmaceutical companies are inclined to use GR powder. Generally, the herb was smashed into super fine powder, mixed with the extract of other herbs and then manufactured to different formulations with excipients in commercial products on market. In that way, are there any differences on bioactivities between GR extract and GR powder? The issue arouses our great interest.

Several studies on pharmacokinetics of gastrodin were reported [20], [21], however, no report on pharmacokinetics of parishin has been published so far. In the present study, a reproducible, rapid, sensitive and selective UHPLC-ESI-MS/MS method for simultaneous determination of gastrodin and parishin in rat plasma was developed for the first time, which was then applied to pharmacokinetics of the two analytes after oral administration of GR extract and GR powder. Moreover, on the basis of the pharmacokinetic parameters of the two analytes, bioavailability values of the two formulations were calculated, which will provide useful information for clinical treatments. To the best of our knowledge, this is the first study on bioavailability comparison between two different medication forms of GR, based on the pharmacokinetics of the two analytes.

Section snippets

Material and reagents

GR was purchased from Tong-Ren-Tang Pharmacy (Beijing, China) in Guiyang city. Half was ground to fine powder (60 mesh) using a common grinder with a knife blade for extraction. Another half was smashed to superfine powder (less than 10–25 μm in diameter) using micronizer in Guizhou Holy Pharmaceutical Co. Ltd. for intragastric administration directly. They were stored at 4 °C before use.

Reference compounds of gastrodin (No. 110807-2002-5) and bergenin (Internal Standard, IS, No. 1532-200202)

Optimization of UHPLC–MS/MS conditions

The selection of the UHPLC–MS/MS conditions was guided with the requirement for obtaining chromatograms with satisfactory resolutions of the analytes and the IS with other endogenous compounds in rat plasma. A few columns were screened before Kinetex XB-C18 column (2.1 mm × 150 mm, 1.7 μm) was finally selected as the column of choice. Different mobile phase were tested. As a result, satisfactory resolution values, sharp and symmetrical peaks were obtained by using acetonitrile–water (containing 0.5%

Conclusion

Firstly, in the present study, an UHPLC–ESI–MS/MS method was developed and validated to determine simultaneously the active compounds gastrodin and parishin in rat plasma for the first time. The described method was sensitive and efficient with a short run time of 10 min and high accuracy that met all requirements in bioanalysis. Sample preparation was simple and reliable. Secondly, the validated method was successfully applied for pharmacokinetics study on the two analytes in rats after oral

Acknowledgments

This work was supported by Sub-project of Key Issues on Deep Development of Pharmaceutical Industry of Gastrodiae Rhizoma (No. 20116005; No. 2011401, 6-1), Guizhou Provincial Special Program on Research and Development of Scientific and Technological Industry about Modernization of TCMs (No. ZY 2011 3013), Guizhou Provincial Program of Science and Technology Innovation Talent Team on Pharmaceutical Analysis (No. 2011 4008), Guizhou Characteristic Key Laboratory of Standardization on Traditional

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    • Rapid authentication of Gastrodiae rhizoma by direct ionization mass spectrometry

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      Studies have revealed that Gastrodiae rhizoma could produce pharmacological effects such as neuroprotection, memory improvement, anti-depressant activity, anti-oxidation, anti-inflammation and could be used for treatment of mental disorder, headache, convulsion, dizziness and paralysis [28–31]. Gastrodin (p-hydroxy-methylphenyl-β-d-glucopyranoside), parishin B/parishin C (bis-[4-(β-D-glucopyranosyloxy)benzyl] citrate) and parishin (tris-[4-(β-D-glucopyranosyloxy)benzyl] citrate) are the major active components of Gastrodiae rhizoma [32–35] that contribute to the pharmacological effects [36–42]. Gastrodin, also called gastrodia elata glycosides, is specified as marker for quality control of Gastrodiae rhizoma [39], with the requirement that the level of gastrodin in Gastrodiae rhizoma should not be less than 0.20% by weight [43].

    • A systematic study of the dissolution and relative bioavailability of four ginsenosides in the form of ultrafine granular powder, common powder and traditional pieces of Panax quinquefolius L, in vitro and in beagles

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    • Comparative pharmacokinetics of gastrodin in rats after intragastric administration of free gastrodin, parishin and Gastrodia elata extract

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      However, previous study (Zhang et al., 2008) just reported the pharmacokinetics of free gastrodin after oral administration of G. elata extract and ignored conversion in vivo from gastrodin conjugates. Although Zhao et al. (2014) has quantified gastrodin and parishin in rat plasma after administration of G. elata extract, the total content of gastrodin, including free gastrodin and that converted from gastrodin conjugates in G. elata extract, was still not analyzed. That is, the dose of G. elata extract administered to rats was determined mainly according to the content of free gastrodin instead of the total content of gastrodin, which might not comprehensively present the metabolic properties of gastrodin in G. elata extract.

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    These authors equally contributed to the manuscript.

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