OBJECTIVETo study different in vivo pharmacokinetic regularity of brucine, total alkaloids of scorched sand-prepared Strychni Semen products and Strychni Semen pulveratum in rats, and probe into mutual impact between single component and compound.

METHODRats in each group were orally administered with brucine, total alkaloids of scorched sand-prepared Strychni Semen products and Strychni Semen pulveratum suspension. The in vivo plasma concentrations of brucine in rats were determined by HPLC. A compartment model was made for the blood drug concentration-time curve using 3P97 software package and the pharmacokinetic parameters of each group were calculated and compared.

RESULTThe in vivo metabolic process of brucine in rats complied with the two-compartment model, weight W = 1/C2. The results of variance analysis showed that among three existing forms of brucine with same dosage, the brucine solution group and the total alkaloids group of scorched sand-prepared Strychni Semen products showed significant differences in C(max), MRT (P < 0.05); and the brucine solution group and the Strychni Semen pulveratum suspension group showed significant differences in C(max), AUC(0-t), and AUC(0-infinity), in which the latter displayed minimum C(max), AUC(0-t) and AUC(0-infinity).

CONCLUSIONThe total alkaloids group of scorched sand-prepared Strychni Semen products showed a relatively longer retention time of effective components of brucine in plasma, while the Strychni Semen pulveratum suspension group showed a lower bioavailability.

Animals ; Male ; Medicine, Chinese Traditional ; Plants, Medicinal ; chemistry ; Rats ; Rats, Sprague-Dawley ; Strychnine ; analogs & derivatives ; pharmacokinetics

OBJECTIVETo prepare brucine stealth liposomes and compare the in vitro characteristics with brucine conventional liposomes.

METHODBrucine stealth liposomes and conventional liposomes were both prepared by ammonium sulfate transmembrane gradients. The encapsulation efficiency, particle size, in vitro release profiles and stability were compared respectively.

RESULTThe encapsulation efficiency of brucine stealth liposomes and conventional liposomes were (80.7 +/- 0.5)%, and (80.5 +/- 0.3)%, respectively. The mean paricle sizes were 103.5 nm and 169. 4 nm, respectively. Whether rat plasma was added or not, the release rate and degree of brucine stealth liposomes were significantly lower than those of conventional liposomes. Brucine stealth liposomes were more stable than conventional liposomes.

CONCLUSIONAs the antitumor durg delivery system, the in vitro characteristics of brucine stealth liposomes are more satisfactory than the corresponding conventional liposomes.

Animals ; Drug Stability ; Drugs, Chinese Herbal ; chemistry ; pharmacokinetics ; Liposomes ; chemistry ; pharmacokinetics ; Particle Size ; Rats ; Strychnine ; analogs & derivatives ; chemistry ; pharmacokinetics

OBJECTIVETo prepare and evaluate brucine-loaded polylacticacid nanoparticles (Bru-PLA-NPs).

METHODThe Bru-PLA-NPs were prepared by solvent diffusion method. The physical, chemical properties and in vitro release behavior of the prepared Bru-PLA-NPs were evaluated, respectively.

RESULTThe mean particle size of the prepared Bru-PLA-NPs was 95 nm with polydispersity index of 0.362. The zeta potential was -15.68 mV. The mean loading and entrapment efficiency of Bru were 7% and 37%, respectively. Compared with Bru solution, an obvious sustained release behavior of Bru from Bru-PLA-NPs was observed in the in vitro release experiment.

CONCLUSIONThe Bru-PLA-NPs prepared by solvent diffusion method exhibit small particle size, high Bru-loading efficiency, and obvious sustained release in vitro

Drug Carriers ; chemistry ; Drug Delivery Systems ; methods ; Drugs, Chinese Herbal ; chemistry ; Kinetics ; Lactic Acid ; chemistry ; Nanoparticles ; chemistry ; Particle Size ; Polyesters ; Polymers ; chemistry ; Strychnine ; analogs & derivatives ; chemistry

OBJECTIVE: To establish a new method for determination of strychnine alkaloid in biological fluids based on molecularly imprinted polymers. METHODS: A strychnine molecularly imprinted monolithic column was prepared by in-situ molecularly imprinted technique. The polymer was filled to a 1cm column, and a method was developed to concentrate and determine strychnine alkaloids in biological fluids. RESULTS: the limit of detection of the method was 4.9 ng, and the recoveries were more than 92%. The relative standard deviations were smaller than 6.59%. The linear correlation coefficients of standard curves were 0.999 1 and 0.9966 respectively. This method was applied to concentrate and determine strychnine in plasma and urine of poisoned rabbit. CONCLUSION The new method could concentrate and simultaneously determine strychnine alkaloids in biological fluids, and it was applied to forensic toxicological analysis.
Alkaloids/analysis* ; Animals ; Chromatography, High Pressure Liquid/methods* ; Humans ; Male ; Polymers/chemistry* ; Rabbits ; Sensitivity and Specificity ; Strychnine/urine*

OBJECTIVE: To establish a liquid chromatography-tandem mass chromatography (LC-MS/MS) method for the simultaneous screening for 22 poisonous alkaloids in blood. METHODS: This method involves a liquid-liquid extraction (LLE) followed by liquid chromatography-tandem mass spectrometry with multi-ple-reaction monitoring (MRM). After blood was extracted with buprenorphine as the internal standard, the target compounds were analyzed with LC-MS/MS-ESI in the positive ionization mode. RESULTS: Identification was based on the compound's retention time and two precursor-to-product ion transitions. The limits of detection ranged from 0.1 ng/mL to 20 ng/mL in blood. CONCLUSION The method was sufficiently selective and sensitive to detect poisonous alkaloids and can be applied in forensic and clinical toxicology.
Aconitine/blood* ; Alkaloids/chemistry* ; Chromatography, Liquid/methods* ; Colchicine/blood* ; Forensic Medicine ; Humans ; Sensitivity and Specificity ; Strychnine/blood* ; Tandem Mass Spectrometry/methods*

OBJECTIVEThis paper reports a HPLC method for determinition of strychnine and brucine in Semen Strychni and its processed products of Jiangxi method and innovated methed.

METHODSiO2 was used as the stationary phase, n-hexane-dichloromethane-methanol-ammonia(47.5:47.5:5:0.35) as the mobile phase, with detection wavelength of 254 nm.

RESULTThe contents of strychnine and brucine in the processed products of Jiangxi are lower.

CONCLUSIONThis method is accurate, simple and reliable.

Chromatography, High Pressure Liquid ; Hot Temperature ; Plants, Medicinal ; chemistry ; Seeds ; chemistry ; Strychnine ; analogs & derivatives ; analysis ; Strychnos nux-vomica ; chemistry ; Technology, Pharmaceutical ; methods

AIMTo study the interaction between strychnine and bovine serum albumin.

METHODSFluorescence spectroscopy and ultraviolet spectroscopy were used.

RESULTSThe static quenching and the non-radiation energy transfer are the two main reasons to leading the fluorescence quenching of BSA. The apparent combining constants (K(A)) between strychnine and BSA are 3.72 x 10(3) at 27 degrees C, 4.27 x 10(3) at 37 degrees C, 4.47 x 10(3) at 47 degrees C and the combining sites are 1.01 +/- 0.03. The combining distance (r = 3.795 nm) and energy transfer efficiency (E = 0.0338) are obtained by Förster's non-radiation energy transfer mechanism.

CONCLUSIONThe interaction between strychnine and BSA was driven mainly by hydrophobic force.

Animals ; Binding Sites ; Cattle ; Energy Transfer ; Plants, Medicinal ; chemistry ; Protein Binding ; Seeds ; chemistry ; Serum Albumin, Bovine ; chemistry ; metabolism ; Spectrometry, Fluorescence ; Spectrophotometry, Ultraviolet ; Strychnine ; chemistry ; metabolism ; Strychnos nux-vomica ; chemistry ; Thermodynamics

OBJECTIVETo compare the pharmaceutical properties and the anti-tumor activities of three kinds of stealth liposomes prepared with different phospholipid composition containing brucine.

METHODStealth liposomes with different phospholipids composition, such as soybean phosphatidycholine (SPC), hydrogenated soybean phosphatidylcholine (HSPC) and the complex of SPC and HSPC, were prepared by ammonium sulfate transmembrane gradient method. Pharmaceutical properties such as shape, encapsulation efficiency and size of three stealth liposomes were compared intensively. Anti-tumor activity of SPC, HSPC and novel stealth liposomes composed of both SPC and HSPC were compared by established mouse liver cancer H22 model. Meanwhile, the mice body weight and immune organ weight were also compared.

RESULTThe encapsulation efficiency of novel, SPC and HSPC stealth liposomes were 77.7%, 64.8% and 74.8%, respectively. The mean diameters of them were less than 100 nm. The tumor inhibition rate of novel, HSPC and SPC stealth liposomes were 57.88%, 49.15%, 23.37%, respectively. The mice body weight, thymus gland index of three stealth liposomes group and spleen index of novel stealth liposomes group had no significant difference with the negative group while SPC and HSPC stealth liposomes group increased the spleen index.

CONCLUSIONPhospholipids composition is the key factor which determines the antitumor activity of brucine-loaded stealth liposomes.

Animals ; Antineoplastic Agents ; chemistry ; pharmacology ; Body Weight ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Humans ; Liposomes ; adverse effects ; chemistry ; Mice ; Particle Size ; Phospholipids ; chemistry ; Strychnine ; analogs & derivatives ; chemistry

OBJECTIVETo compare the pharmacokinetic characteristics of brucine following intravenous administration of liposomes, containing total alkaloids from seed of Strychnos nux-vomica, to rats with different phospholipids composition.

METHODLiposomes containing the total alkaloids were prepared by the method of ammonium sulfate transmembrane gradients and stealth liposome technique. The contents of total alkaloids and brucine in liposomes were determined and compared after free drug being removed. After intravenous administration of total alkaloids solution or liposomes with different composition, plasma samples were drawn at predetermined time points and the concentrations of brucine were determined by a validated method of HPLC. Pharmacokinetic analysis was performed by 3P97 program.

RESULTThe ratios of brucine to total alkaloids in liposomes hardly varied with phospholipids composition. Compared with SPC liposome, AUC of brucine was increased 13.3-fold and apparent volume of distribution was decreased to only 3.6% following intravenous administration of HSPC liposome. In addition, besides that AUC of brucine was slightly increased, most pharmacokinetic parameters were not significantly changed after administration of the novel liposome compared with those of SPC liposome.

CONCLUSIONPhospholipids composition has a significant influence on the pharmacokinetics of brucine after intravenous administration of liposomes containing total alkaloids from seed of S. nux-vomica.

Alkaloids ; administration & dosage ; pharmacokinetics ; Animals ; Drugs, Chinese Herbal ; administration & dosage ; pharmacokinetics ; Infusions, Intravenous ; Liposomes ; administration & dosage ; pharmacokinetics ; Male ; Models, Animal ; Rats ; Rats, Sprague-Dawley ; Seeds ; chemistry ; Strychnine ; administration & dosage ; analogs & derivatives ; pharmacokinetics ; Strychnos nux-vomica ; chemistry

Because of its officinal value, strychnos is widely used by clinic and individual. Since toxic dose and therapeutic dose are very close, strychnos poisoning cases are frequently reported. In this paper the chemical component, toxic dose, mechanisms of toxicity, poisoning symptom and pathological changes after strychnos poisoning are reviewed.
Alkalies/poisoning* ; Animals ; Central Nervous System/drug effects* ; Dose-Response Relationship, Drug ; Forensic Medicine ; Humans ; Immune System/drug effects* ; Lethal Dose 50 ; Plants, Medicinal/chemistry* ; Seeds/chemistry* ; Strychnine/poisoning* ; Strychnos/toxicity*