A simple, rapid and high sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the determination of neostigmine in small-volume beagle dog plasma was developed to assess the plasma pharmacokinetics of neostigmine. After protein precipitation in a Sirocco 96-well filtration plate, the filtrate was directly injected into the LC-MS/MS system. The analytes were separated on a Hanbon Hedera CN column (100x4.6 mm, 5 mu m) with a mobile phase composed of methanol-water (60:40, v/v) and the water containing 0.01% formic acid at a flow rate of 0.6mL/min, with a split ratio of 1:1 flowing 300 L into the mass spectrometer. The run time was 3 min. Detection was accomplished by electrospray ionization source in multiple reactions monitoring mode with the precursor-to-product ion transitions m/z 223.072.0 and 306.0140.0 for neostigmine and anisodamine (internal standard), respectively. The method was sensitive with a lower limit of quantitation of 0.1 ng/mL, and good linearity in the range 0.1-100ng/mL for neostigmine (r0.998). All the validation data, such as accuracy, intra-run and inter-run precision, were within the required limits. The method was successfully applied to pharmacokinetic study of neostigmine methylsulfate injection in beagle dogs. Copyright (c) 2013 John Wiley & Sons, Ltd.
The stability constants of the binary ML2+ and ternary M(ATP)L2- complexes, where L=Iq (isoquinoline) or BIm (benzimidazole) and M=Zn2+ or Cd2+, have been determined by potentiometric pH titration in aqueous solution at I=0.1 mol/L (NaClO4), T=25 degrees C. The stability of the ternary complexes characterized by Delta logK(M)=logK(M(ATP)L)(M(ATP))-logK(ML)(M) corresponding to the equilibrium M(ATP)(2-) + ML2+ = M(ATP)L2- + M2+ is higher than what would be expected on statistical grounds. The increase may be related to the stacking interaction between the aromatic ring of the ligands L and the purine moiety of ATP(4-). H-1 NMR studies of Zn2+/ATP(4-)/L confirm the presence of stacking in the ternary complexes. It is concluded that the strength of the intramolecular stacking interaction is dependent on the structure of the aromatic ring of the ligand L and the formation of a metal ion bridge. Possible implications are discussed briefly.
Ye, Xiaolan;Cao, Di;Zhao, Xin;Song, Fenyun;Huang, Qinghua;Fan, Guorong*;Wu, Fuhai*
Journal of chromatography. B, Analytical technologies in the biomedical and life sciences,2014年970:108-120 ISSN：1570-0232
Fan, Guorong;Wu, Fuhai
[Ye, Xiaolan; Huang, Qinghua; Cao, Di; Wu, Fuhai; Song, Fenyun] Department of Pharmaceutical Analysis, School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, China;[Ye, Xiaolan; Fan, Guorong; Cao, Di; Zhao, Xin] Shanghai Key Laboratory for Pharmaceutical Metabolite Research, No. 325 Guohe Road, Shanghai, China;[Ye, Xiaolan; Fan, Guorong; Cao, Di; Zhao, Xin] Department of Pharmaceutical Analysis, School of Pharmacy, Second Military Medical University, No. 325 Guohe Road, Shanghai, China;[Wu, Fuhai] School of Public Health, Guangdong Key Laboratory of Molecular Epidemiology, Guangdong Pharmaceutical University, Guangzhou, China
[Fan, Guorong] Shanghai Key Laboratory for Pharmaceutical Metabolite Research, No. 325 Guohe Road, Shanghai 200433, PR China. Electronic address:;[Wu, Fuhai] School of Public Health, Guangdong Key Laboratory of Molecular Epidemiology, Guangdong Pharmaceutical University, Guangzhou 510310, PR China. Electronic address:
Journal of ethnopharmacology,2017年210:242-253 ISSN：0378-8741
Song, Fenyun;Gao, Xiaoxia
[Chen, Xiaodong; Feng, Meirou; Liu, Shaofeng; Fan, Yunfei] College of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, PR China;[Chen, Xiaodong] Sirio Pharm CO., LTD, Shantou 515041, PR China;[Gao, Xiaoxia] College of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, PR China. Electronic address: firstname.lastname@example.org;[Liu, Shaofeng] Department of Pharmacy, Hezhou City People's Hospital, Hezhou, 542800, PR China;[Song, Fenyun] College of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, PR China. Electronic address: email@example.com
[Song, Fenyun; Gao, Xiaoxia] College of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, PR China. Electronic address:
ETHNOPHARMACOLOGICAL RELEVANCE: The dried ripe seeds of Nux Vomica (Strychnos nux-vomica L.), a traditional Chinese medicine, have been used to treat multifarious symptoms. However, the clinical applications of Nux Vomica are limited by its severe toxicity. In this study, Nux Vomica was subjected to nuclear magnetic resonance (NMR) metabonomics and pathological examination to determine relevant biomarkers in target organs and to explain the underlying toxicity mechanism. MATERIALS AND METHOD: Thirty-six male Sprague-Dawley rats were randomly divided into three groups of twelve rats. The control group was oral gavaged with distilled water, and two experiment groups were treated with Nux Vomica at a dose of 0.315 and 0.630g/kg body weight. On days 14 and 21, serum, urine, liver and kidney tissues were collected for histopathological examination, biochemical analysis and 1H-NMR analysis. RESULTS: The metabolites changes of rats treated with Nux Vomica are obviously differ from that of controls. In serum, low-dose group compared with control shows the significantly changes included elevated concentration of glucose, TMAO, and creatine, with decreased lipids, 3-HB, lactate, and unsaturated fatty acid. Change in taurine was only observed in the separation comparison of high-dose group and control. In urine, the variation metabolites included elevations in glucose, creatine, and TMAO as well as decreased lactate, succinate, alpha-ketoglutaric acid, citrate and hippurate in low-dose group compared with control. Only alanine and creatine were decreased significantly in high-dose group compared with control. CONCLUSION: Nux Vomica induced disruptions in glycolysis, lipid and amino acid metabolism, and toxic effects were aggravated in liver and kidney tissues as dosing time was prolonged. 1H-NMR-based metabonomics combined with biochemical and histopathological methods can be applied to elucidate the toxicity mechanism of Nux Vomica decoction that caused liver and kidney injuries in rats.