Development and validation of an LC‐MS/MS method for the determination of bullatine A in rat plasma: application to a pharmacokinetic study

Teng, Shiyong; Zhang, Sixi; Niu, Kai; Li-Jie, Zhai; Wang, Shiji

doi:10.1002/bmc.3498

Cited by 5 publications

(3 citation statements)

References 6 publications

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“…Freeze–thaw stability was investigated after three complete freeze–thaw cycles (–60 to 25°C) on consecutive days. Post‐preparative stability was assessed by analyzing the ready‐to‐inject samples placed in autosampler at 4°C for 10 h. The stability of the IS (200 ng/mL) was also examined with a similar method (Teng et al , ; Deng et al , ).…”

Section: Methodsmentioning

confidence: 99%

Determination and validation of chikusetsusaponin IVa in rat plasma by UPLC‐MS/MS and its application to pharmacokinetic study

Wang

Liu

Guo

et al. 2016

Biomedical Chromatography

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A novel, sensitive and rapid ultra-performance liquid chromatography-tandem mass spectrometric method for the quantification of chikusetsusaponin IVa (CHS-IVa) in rat plasma was established and validated. Plasma samples were pre-treated by precipitation of protein with acetonitrile and chromatographed on a Waters Symmetry C18 analytical column (4.6 × 50 mm, i.d., 3.5 μm) using a mobile phase consisting of methanol and water containing 0.05% formic acid (55:45, v/v) at a flow rate of 0.4 mL/min. The deprotonated molecular ions [M - H](-) were employed in electrospray negative ionization mode and selected reaction monitoring transitions were performed for detection. The calibration curves exhibited good linearity (r > 0.99) over the range of 0.5-1000 ng/mL for CHS-IVa. The recoveries of CHS-IVa were >92.5% and exhibited no severe matrix effect. This method was successfully applied in the pharmacokinetic study of CHS-IVa in rats. For oral administration, the plasma concentrations of CHS-IVa increased to a peak value at 0.35 ± 0.14 h, followed by a gradual decrease to the lower limit of quantitation in 24 h. For intravenous administration, the plasma concentrations of CHS-IVa decreased quickly (t1/2 , 1.59 ± 0.25 h). The absolute bioavailability of CHS-IVa in rats was 8.63%. Copyright © 2016 John Wiley & Sons, Ltd.

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Section: Methodsmentioning

confidence: 99%

Determination and validation of chikusetsusaponin IVa in rat plasma by UPLC‐MS/MS and its application to pharmacokinetic study

Wang

Liu

Guo

et al. 2016

Biomedical Chromatography

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“…As a principal group of compounds present in Aconitum , approximately 170 alkaloids have been identified and fell into four skeletal categories: C 18 -, C 19 -, C 20 - and bis -diterpenoid alkaloids [3–5]. Bullatine A, a C 20 -diterpenoid alkaloid, is one of the major effective and quality control ingredients identified from A. brachypodi Radix [6]. The chemical structures of C 18 -, C 19 -, and C 20 -diterpenoid alkaloids, as well as bullatine A, are presented in Fig.…”

Section: Introductionmentioning

confidence: 99%

Bullatine A stimulates spinal microglial dynorphin A expression to produce anti-hypersensitivity in a variety of rat pain models

Huang

Mao

et al. 2016

J Neuroinflammation

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BackgroundAconiti brachypodi Radix (Xue-shang-yi-zhi-hao) has been prescribed to manage chronic pain, arthritis, and traumatic injuries. Bullatine A, a C20-diterpenoid alkaloid, is one of its principle effective compounds. This study aimed to investigate the anti-hypersensitivity of bullatine A in a variety of rat pain models and explore its mechanisms of action.MethodsRat neuropathic pain, inflammatory pain, diabetic neuropathic pain, and bone cancer pain models were used. Dynorphin A and pro-inflammatory cytokines were measured in the spinal cord and cultured primary microglia. Double immunofluorescence staining of dynorphin A and glial and neuronal cellular markers was also measured in the spinal cord.ResultsSubcutaneous and intrathecal injection of bullatine A dose-dependently attenuated spinal nerve ligation-, complete Freud’s adjuvant-, diabetes-, and bone cancer-induced mechanical allodynia and thermal hyperalgesia, with the efficacies of 45–70 % inhibition, and half-effective doses of 0.9–1.9 mg/kg for subcutaneous injection. However, bullatine A was not effective in blocking acute nociceptive response in the normal condition. Bullatine A specifically stimulated dynorphin A expression in microglia in the spinal cord in vivo and cultured primary microglia in vitro; the stimulatory effects were completely inhibited by the microglial inhibitor minocycline. In contrast, bullatine A did not have an inhibitory effect on peripheral nerve injury- or lipopolysaccharide-induced pro-inflammatory cytokine expression. The spinal anti-allodynic effects of bullatine A were entirely blocked by intrathecal injection of minocycline, the specific dynorphin A antiserum, and the selective k-opioid receptor antagonist.ConclusionsWe, for the first time, demonstrate that bullatine A specifically attenuates pain hypersensitivity, regardless of the pain models employed. The results also suggest that stimulation of spinal microglial dynorphin A expression mediates bullatine A anti-nociception in pain hypersensitivity conditions.

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“…Precision was expressed in terms of percentage coefficient of variation (CV) and was calculated based on the quotient between the standard deviation and the mean for each concentration level. Accuracy was expressed in terms of percentage bias and was calculated according to the difference between the determined concentration and the spiked concentration of the samples (Teng et al, ).…”

Section: Methodsmentioning

confidence: 99%

Pharmacokinetics and metabolism study of veratramine in mice after oral administration using LC‐MS/MS

Zhang

et al. 2016

Biomedical Chromatography

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A simple and sensitive high-performance liquid chromatography coupled with hybrid triple quadrupole-linear ion trap mass spectrometry (Q-trap-MS) method was developed and validated for the determination of veratramine, the major bioactive and neurotoxic component in Veratrum nigrum L. Veratramine and the internal standard (IS) were separated with a Waters Symmetry C18 column and eluted with a gradient mobile phase system containing acetonitrile and 0.1% aqueous formic acid. The analysis was performed by using positive electrospray ionization mode with multiple reaction monitoring (MRM). Transition ions of m/z 410.2 → 295.2 for veratramine and m/z 426.1 → 113.8 for the IS were monitored. The method was validated with a good linearity in the range of 1-1000 ng/mL and lower limit of quantification of 1 ng/mL. The precision (CV) of intra- and inter-day ranged from 3.92 to 7.29%, while the accuracy (bias) intra- and inter-day were between -4.78 and 1.65%. The recovery, stability and matrix effect were within the acceptable ranges. Five metabolites of veratramine, including four hydroxylated and one sulfated metabolites, were tentatively identified using predictive MRM-information dependent acquisition-enhanced product ion mode (predictive MRM-IDA-EPI). The developed method was successfully applied to the pharmacokinetic and metabolic study of veratramine in mice after oral administration of veratramine. Copyright © 2016 John Wiley & Sons, Ltd.

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Development and validation of an LC‐MS/MS method for the determination of bullatine A in rat plasma: application to a pharmacokinetic study

Cited by 5 publications

References 6 publications

Determination and validation of chikusetsusaponin IVa in rat plasma by UPLC‐MS/MS and its application to pharmacokinetic study

Determination and validation of chikusetsusaponin IVa in rat plasma by UPLC‐MS/MS and its application to pharmacokinetic study

Bullatine A stimulates spinal microglial dynorphin A expression to produce anti-hypersensitivity in a variety of rat pain models

Pharmacokinetics and metabolism study of veratramine in mice after oral administration using LC‐MS/MS

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