OBJECTIVETo study the processing principles of different processed products of Aconitum pendulum.

METHODUsing high performance liquid chromatography and acute toxicity test to compare the changes in chemical composition and toxicity of the roots and processed products of A. pendulum.

RESULTThe main toxic components of the roots of A. pendulum were aconitine, deoxyaconitine and 3-acetylaconitine. The contents of these three alkaloids were significantly reduced in processed products, while benzoylaconitine significantly increased. In addition, processed products emerged aconine, polyschistine-D, beyzoyldeoxyaconine, 16-epi-pyroaconitine and 16-epi-pyrodeoxyaconitine. From the structural analysis, these new emerged compounds transformed from the aconitine, deoxyaconitine and 3-acetylaconitine.

CONCLUSIONDifferent processing methods can reduce the toxicity of the roots of A. pendulum. Processing principle is ester hydrolysis and high-temperature pyrolysis.

Aconitine ; analogs & derivatives ; analysis ; Aconitum ; chemistry ; toxicity ; Animals ; Female ; Male ; Mice

This paper is aim to investigate the pharmacokinetics and absolute bioavailability of neoline in Beagle dogs, and provide a theoretical basis for further study. Ethyl acetate was used for liquid-liquid extracting after 10% ammonia alkalizing. The method of UPLC-Q-TOF-MS was established for the determination of neoline plasma concentrations. Beagle dogs were orally or intravenously administered with neoline for pharmacokinetic and absolute bioavailability study. Good linear relationship of neoline was found over the range of 0.1-4 mg x L(-1) (R2 = 0.9982) and 2-100 microg x L(-1) (R2 = 0.9945). Intra-and inter-day precision, expressed as the relativestandard (RSD) were less than 5.0%. Accuracy, expressed as the relative error (RE) was within 90.0%-115%. The recovery of neoline in dog plasma was more than 80%. After 6 mg x kg(-1) for ig and 1 mg x kg(-1) for iv administration of neoline, the main pharmacokinetic parameters were analyzed with Winnonlin software. t(1/2) were (313.88 +/- 63.18), (236.33 +/- 229.84) min, and AUC(0-infinity) were (58,027.40 +/- 14,132.69), (473,578.02 +/- 82,333.08) min x microg x L(-1) for ig and iv administration respectively. The absolute bioavail ability was (73.15 +/- 10.29) %. The method of UPLC-Q-TOF-MS described in the report was sensitive, reliable and specific, and suitable for pharmacokinetic study of neoline in Beagle dog. The high absolute bioavailability of neoline in dog suggested good absorption of neline which was worth of further investigation.
Aconitine ; analogs & derivatives ; chemistry ; pharmacokinetics ; Animals ; Biological Availability ; Dogs ; Drug Stability ; Female ; Male

OBJECTIVES: To explore the possible mechanism of Yunaconitine poisoning by studying the changes of urine metabolic profile in rats chronically poisoned by Yunaconitine via non-targeted metabolomics. METHODS: A rat model of Yunaconitine poisoning was established, and a metabolomics method based on UPLC-QTOF-MS technology was used to obtain the urine metabolic profile. Principal component analysis (PCA), orthogonal projections to latent structures-discriminant analysis (OPLS-DA), variable importance in projection (VIP) value greater than 1, fold change (FC) value greater than 3 or less than 0.33 and P value less than 0.05 were used to screen potential biomarkers related to the toxicity of Yunaconitine. The metabolic pathway analysis was performed through the MetaboAnalyst website and pathological changes of related tissues were observed. RESULTS: Sixteen potential biomarkers including L-isoleucine were screened, which mainly involved six metabolic pathways including the biosynthesis and degradation of valine, leucine and isoleucine, pentose and glucuronate interconversions, and propanoate metabolism, alanine, aspartate and glutamate metabolism, tyrosine metabolism. Pathological studies showed that rat toxic change in nervous system, liver and cardiac caused by Yunaconitine. CONCLUSIONS Yunaconitine may cause neurotoxicity, hepatotoxicity and cardiotoxicity by affecting amino acid and glucose metabolism.
Aconitine/analogs & derivatives* ; Animals ; Biomarkers/metabolism* ; Chromatography, High Pressure Liquid ; Metabolome ; Metabolomics ; Rats

To investigate the chemical constituents of the roots of Aconitum taipaicum, silica gel column chromatography was used for the isolation and purification of compounds. A new norditerpenoid alkaloid, isodelelatine (1), along with five known alkaloids, atisine (2), delfissinol (3), liangshanine (4), hypaconitine (5) and delelatine (6) were isolated and identified. The structure of the new compound was elucidated on the basis of spectral data.
Aconitine ; analogs & derivatives ; chemistry ; isolation & purification ; Aconitum ; chemistry ; Alkaloids ; chemistry ; Diterpenes ; chemistry ; Molecular Structure ; Plant Roots ; chemistry ; Plants, Medicinal ; chemistry

OBJECTIVETo find out hydrolysis regularity of aconitine.

METHODAconitine was air-tighted and hydrolyzed in water for 8, 12, 16, 20, 24 h. The hydrolysis products were analyzed by HPLC-MS. A major hydrolysis product was isolated by alumina oxide column chromatography, and identified by 1H and 13C-NMR spectra.

RESULTHPLC-MS analysis shows that the major hydrolysis products are benzoylaconine and aconine. The hydrolysis can mostly be completed within 20 hours.

CONCLUSIONDiester aconitum alkaloid can be changed to monoester aconitum and aconine alkaloids. Under the controled condition benzoylaconine is a major hydrolysis products.

Aconitine ; analogs & derivatives ; chemistry ; isolation & purification ; Chromatography, High Pressure Liquid ; methods ; Hydrolysis ; Spectrometry, Mass, Electrospray Ionization ; Water ; chemistry

To establish a method for the content determination of indexes for measuring aconitic compounds contained in Shenfu injection, in order to provide basis for the evaluation of the curative effect of monkshood in Shenfu injection. The sample were purified and enriched with HF-LPME. ACQUITY UPLC BEH C18 column (2.1 mm x 50 mm, 1.7 microm) was adopted and eluted with a gradient program, with acetonitrile-10 mmol x L(-1) NH4HCO3 (pH 10) as the mobile phases. The flow rate was 0.45 mL x min(-1). The content was determined with ESI and MRM. The results showed that aconitine, hypaconitine and mesaconitine showed a good linear relationship, with r > 0.999, within the range of 0.1-100 ng x L(-1). The recoveries were detected to be 100.1%, 97.4%, 97.5%, with RSD being 1.2%, 1.1%, 1.5%, respectively. This method was used to prove the safety of Shenfu injection, and provide scientific basis for correct evaluation of curative effect of monkshood, as well as a reliable, simple and practical means for quality control of monkshood-containing Chinese materia medica preparations.
Aconitine ; analogs & derivatives ; analysis ; Chromatography, High Pressure Liquid ; methods ; Drugs, Chinese Herbal ; analysis ; Mass Spectrometry ; methods ; Quality Control

OBJECTIVETo investigate the effects of different kinds and concentration of transdermal enhancers on Lappaconitine transcutaneous permeation when used individually or together.

METHODUsing modified Franz-type diffusion cell and excised human body skin as an in vitro transdermal model, the concentration of lappaconitine was determined by HPLC, then cumulative permeation quantity (Q) and stability rate (J) of progesterone were calculated.

RESULTPenetration enhancers such as propylene glycol, dodecanol, IPM, and particularly 3% OA and Azone, can significantly enhance the penetration rate of lappaconitine. Concentration effect of penetration enhancers concentration on lappaconitine transcutaneous permeation were found in experiments, the permeation effect of Azone was better than Azone + OA and Azone + propylene glycol.

CONCLUSIONThe transdermal rate of lappaconitine from batch which contains 3% OA or Azone is higher than others. Combination of Azone with other penetration enhancers is not recommended for Lappaconitine transcutaneous permeation.

Aconitine ; analogs & derivatives ; metabolism ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal ; metabolism ; Humans ; Permeability ; drug effects ; Skin ; cytology ; metabolism

OBJECTIVETo set up a capillary electrophoresis method with field-amplified sample injection for the determination f aconitine and hypaconitine in Gucixiaotong Ye.

METHODAn uncoated fused-silica capillary column (50 microm x 50 cm, effective length 42 cm) was used as the separation channel. The running buffer was 50 mmol x L(-1) phosphate electrolyte solution (pH 9)-m nol (90:10) , the running voltage was 10 kV and the capillary inlet was dipped in methanol for 5 s prior to electrokinetic injection (12 kV, 30 s), the detection wavelength was set at 235 nm.

RESULTAconitine and hypaconitine were linear in the concentration ranges of 17.2-275 microg x L(-1) and 34. 4-550 microg x L(-1), respectively. The average recovery was more than 93.9% with the RSD of 3.8%. This method could enrich 500 fold of aconitine alkaloid.

CONCLUSIONThe method is simple, rapid and specific with high stacking efficiency, it provides a new reliable means for production and quality control of Gucixiaotong Ye.

Aconitine ; analogs & derivatives ; analysis ; isolation & purification ; Buffers ; Electricity ; Electrophoresis, Capillary ; methods ; Hydrogen-Ion Concentration ; Injections ; Solutions ; Time Factors

AIMTo identify the main metabolites of aconitine in the urine of rabbits.

METHODSAfter oral administration of aconitine (5 mg.kg-1), the urine of male rabbits was collected and extracted by solid phase extraction and analyzed by liquid chromatography-ion trap mass spectrometry.

RESULTSAconitine and 4 metabolites were found in the rabbit urine. Their protonated molecular ions at m/z 632, m/z 604, m/z 590, m/z 500 and multistage fragment ions with neutral loss of 60 u, 32 u, 28 u and 18 u were monitored. Their relative concentration were M1 > Aconitine > M4 > M2 > M3.

CONCLUSIONThe metabolites M1-M4 were deduced as 16-O-demethylaconitine, benzoylaconine, 16-O-demethylbenzoylaconine and aconine, respectively.

Aconitine ; analogs & derivatives ; metabolism ; urine ; Alkaloids ; urine ; Animals ; Chromatography, High Pressure Liquid ; Male ; Rabbits ; Spectrometry, Mass, Electrospray Ionization

This paper aims to study the difference in the intestinal absorption kinetics of main active components of Sini decoction and its separated recipes and explain the scientificity and rationality of the compatibility of Sini Decoction. A in situ intestinal perfusion rat model was established to evaluate the differences in the absorption of benzoylmesaconine, benzoylaconine, benzoylhypacoitine, mesaconitine, hypaconitine, glycyrrhizic acid, liquiritin and 6-gingerol from Sini Decoction and its separated recipes in the duodenum, jejunum and ileum by high performance liquid chromatography(HPLC). The results indicated that the Sini Decoction group was superior to the Aconiti Lateralis Radix Praeparata group in terms of absorption degree and rate for aconitum alkaloids. The absorption of benzoylmesaconine and hypaconitine in the duodenum, jejunum and ileum was faster and stronger in the Sini Decoction group(P<0.05). The absorption degree of glycyrrhizic acid in the duodenum was significantly higher in the Sini Decoction group than in the Glycyrrhizae Radix et Rhizoma group and the Glycyrrhizae Radix et Rhizoma-Zingiberis Rhizoma group(P<0.05). The absorption rate and degree of 6-gingerol in the ileum in the Sini Decoction group were significantly higher than those in the Zingiberis Rhizoma group(P<0.05). In short, Zingiberis Rhizoma and Glycyrrhizae Radix et Rhizoma can promote the absorption of aconitum alkaloids in different intestinal segments, which reflects the scientific composition of Sini Decoction.
Aconitine/analogs & derivatives* ; Aconitum ; Alkaloids ; Animals ; Catechols ; Drugs, Chinese Herbal ; Fatty Alcohols ; Glycyrrhizic Acid ; Intestinal Absorption ; Kinetics ; Rats