Liquid chromatographic–tandem mass spectrometric method for the quantitation of huperzine A in dog plasma

Wang, Yingwu; Chu, Dafeng; Gu, Jingkai; Fawcett, J. Paul; Wu, Yi; Liu, Wanhui

doi:10.1016/j.jchromb.2004.01.013

Cited by 28 publications

(27 citation statements)

References 6 publications

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“…Autoradiographic studies in mice showed that HupA was present in all regions of the brain, but was particularly concentrated in the frontoparietal cortex, striatal cortex, hippocampus, and nucleus accumbens after iv injection [32] . The plasma concentration-time curves of HupA in dogs were determined by using the liquid chromatography-mass spectrum-mass spectrum (LC-MS-MS) method after the last intramuscular injection (10 µg/kg per day for 15 d) of a sustained-release formulation, and the mean C max was 0.36±0.08 ng/mL, which occurred at 48.0±24.5 h. The mean plasma elimination half-life was 54.8±5.6 h, and the mean area under the plasma concentration versus time curve was 92.6±4.5 ng· h/mL [142] . A pharmacokinetic study using HupA transdermal patches in 6 beagle dogs showed that the HupA patches were able to deliver sustained or controlled drug release in vivo.…”

Section: Pharmacokineticsmentioning

confidence: 99%

Progress in studies of huperzine A, a natural cholinesterase inhibitor from Chinese herbal medicine1

Rui

Yan

Tang

2006

Acta Pharmacologica Sinica

416

223

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Huperzine A (HupA), a novel alkaloid isolated from the Chinese herb Huperzia serrata, is a potent, highly specific and reversible inhibitor of acetylcholinesterase (AChE). Compared with tacrine, donepezil, and rivastigmine, HupA has better penetration through the blood-brain barrier, higher oral bioavailability, and longer duration of AChE inhibitory action. HupA has been found to improve cognitive deficits in a broad range of animal models. HupA possesses the ability to protect cells against hydrogen peroxide, β-amyloid protein (or peptide), glutamate, ischemia and staurosporine-induced cytotoxicity and apoptosis. These protective effects are related to its ability to attenuate oxidative stress, regulate the expression of apoptotic proteins Bcl-2, Bax, P53, and caspase-3, protect mitochondria, upregulate nerve growth factor and its receptors, and interfere with amyloid precursor protein metabolism. Antagonizing effects of HupA on N-methyl-D-aspartate receptors and potassium currents may also contribute to its neuroprotection as well. Pharmacokinetic studies in rodents, canines, and healthy human volunteers indicated that HupA was absorbed rapidly, distributed widely in the body, and eliminated at a moderate rate with the property of slow and prolonged release after oral administration. Animal and clinical safety tests showed that HupA had no unexpected toxicity, particularly the dose-limiting hepatotoxicity induced by tacrine. The phase IV clinical trials in China have demonstrated that HupA significantly improved memory deficits in elderly people with benign senescent forgetfulness, and patients with Alzheimer disease and vascular dementia, with minimal peripheral cholinergic side effects and no unexpected toxicity. HupA can also be used as a protective agent against organophosphate intoxication.

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Section: Pharmacokineticsmentioning

confidence: 99%

Progress in studies of huperzine A, a natural cholinesterase inhibitor from Chinese herbal medicine1

Rui

Yan

Tang

2006

Acta Pharmacologica Sinica

416

223

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“…To date, the analytical methods used for the determination of huperzine A in biological fluids have included high-performance liquid chromatography (HPLC) with ultraviolet (UV) detection or diode array (7,8). Huperzine A levels in blood samples from dogs and rats have also been analyzed by HPLC with ultraviolet detection and tandem mass spectrometry (9-11).…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetics of huperzine A following oral administration to human volunteers

Zhang

et al. 2007

Eur. J. Drug Metabol. Pharmacokinet.

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The objective of the present study was to investigate the in vivo pharmacokinetics of huperzine A in healthy human volunteers. Twelve subjects (M 6, F 6; age ranged from 20-25 years) participated in the study. Huperzine A was administered in tablet form at a single dose of 0.4 mg. Following oral administration, the presence of huperzine A started to appear in the plasma at 5-10 min, and reached the peak concentrations with a Cmax of 2.59 +/- 0.37 ng/ml at 58.33 +/- 3.89 min (time to reach peak level, Tmax. The area under plasma vs time curve (AUC(0-t)) and the area under plasma from zero to infinity (AUC(0-infinity) for huperzine A were found to be 1986.96 +/- 164.57 microg/l.min and 2450.34 +/- 233.32 microg/l.min, respectively. The results of this study indicated that the pharmacokinetics of huperzine A conformed to a two-compartmental open model. The mean values of alpha and the beta half-life were 21.13 +/- 7.28 min and 716.25 +/- 130.18 min respectively, and showed a biphasic profile with rapid distribution followed by a slower elimination rate.

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“…Only Nucleosil C18 column could do the task. However, the difference in retention time between HupA and B was very small, only 0.05 min [18].…”

Section: Comparison Of Analytical Hplc Between C18mentioning

confidence: 85%

“…In some cases, changes in the stationary phase may be rather useful than the mobile-phase composition to achieve the desired separation. In previous works, the separation factors of HupA and HupB were quite low in analytical HPLC using C18 as the stationary phases, although the chromatographic conditions were optimized and additives were included in the mobile phases [17,18]. Therefore, for resolution of the two compounds, other stationary phase could be a better alternative.…”

Section: Introductionmentioning

confidence: 99%

A cyanopropyl reversed phase chromatography enables resolution of huperzine A and B on analytical and preparative scales

Sun

Zhang

et al. 2005

J of Separation Science

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Huperzine A (HupA) and huperzine B (HupB) are two medically important components of Huperzia serrata. It is difficult to obtain high yields of the separation from the plant using conventional liquid extraction and chromatography. However, this study has found that RP chromatography with cyanopropyl (CN) medium was able to separate these two analogs simultaneously from the plant extract with higher resolution. Comparison between a CN medium and a popular C18 medium demonstrated the superiority of the CN over the C18 in resolution for both analytical and preparative separation of HupA and HupB. A preparative process was developed for simultaneous purification of HupA and HupB from H. serrata. The yields on the basis of the mass of the herbal powder for HupA and HupB were 0.019 and 0.008% respectively, which were about 1.9 and 10 times of those reported in the literature.

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Liquid chromatographic–tandem mass spectrometric method for the quantitation of huperzine A in dog plasma

Cited by 28 publications

References 6 publications

Progress in studies of huperzine A, a natural cholinesterase inhibitor from Chinese herbal medicine1

Progress in studies of huperzine A, a natural cholinesterase inhibitor from Chinese herbal medicine1

Pharmacokinetics of huperzine A following oral administration to human volunteers

A cyanopropyl reversed phase chromatography enables resolution of huperzine A and B on analytical and preparative scales

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