OBJECTIVETo study the absorption characteristics of alkaloids in Coptis chinensis in rat intestinal.

METHODIn situ single-pass perfused rat intestinal model was used and the concentrations of berberine and palmatine were determined by HPLC, the drug absorption rate constant (K(a)) and apparent absorption coefficient (P(app)) were tested to evaluate their absorption characteristics.

RESULTThe absorption of berberine and palmatine in different regions of rat intestinals was significantly different. From bigness to smallness, the P(app) value of berberine at 50 mg x L(-1) were ileum, duodenum, jejunum and colon, of palmatine at 50 mg x L(-1) were ileum, colon, jejunum and duodenum. The concentration of berberine and palmatine had distinctive effect on the K(a) value of berberine and palmatine were ordered from larger to little as in Wujiwan compatibility, Coptis chinensis extractive and single compound.

CONCLUSIONThe berberine and palmatine were absroped at all regions of rat intestinal. The absorption characteristics of 2 alkaloids were not passive diffusion. The other ingredients in Wujiwan compatibility and Coptis chinensis extractive could promote the absorption of alkaloids.

Alkaloids ; pharmacokinetics ; Animals ; Berberine ; pharmacokinetics ; Berberine Alkaloids ; pharmacokinetics ; Coptis ; Intestinal Absorption ; Male ; Perfusion ; Rats ; Rats, Wistar

OBJECTIVEDevelop an LC-MS method to determine evodiamine and rutaecarpine in rats plasma simultaneously. The method was employed to investigate pharmacokinetics of evodiamine and rutaecarpine.

METHODBlood samples were collected in different time after oral administrated with the extracts of Euodiae Fructus, the plasma concentration of evodiamine and rutaecarpine was determined by LC-MS, pharmacokinetic parameters were calculated by WinNonlin 5.1 software.

RESULTThe linear ranges of evodiamine and rutaecarpine were 0.5-100 microg x L(-1) (r = 0.995 9), 1-200 microg x L(-1) (r = 0.999 3) respectively. The average recovery were exceeded 76% (n = 5), the precision of inner-day and inter-day were less than 15%. The pharmacokinetics parameters AUC, t1/2, CL _F of evodiamine were: (2 215.24 +/- 414.49), (4 230.62 +/- 753.77), (13 219.21 +/- 3 740.95) min x ng(-1) x mL(-1); (146.57 +/- 38.38), (114.38 +/- 14.65), (163.37 +/- 8.83) min; (184 607.29 +/- 32 502.21), (192 878.22 +/- 31 897.37), (19 3224.63 +/- 62 278.74) mL x min(-1). The pharmacokinetics parameters AUC, t1/2, CL_F of rutaecarpine were (2 283.53 +/- 298.51), (4 424.84 +/- 276.95), (14 239.93 +/- 3648.27) min x ng(-1) x mL(-1); (167.10 +/- 15.82), (131.58 +/- 20.07), (144.41 +/- 13.65) min; (1 177 340.54 +/- 2 4942.21), (181 262.92 +/- 11 162.22), (177 508.10 +/- 52 611.80) mL x min(-1).

CONCLUSIONThe method described in this report has high sensitivity and selectivity, and was suitable for pharmacokinetic studies of evodiamine and rutaecarpine. The kinetic process of evodiamine and rutaecarpine in rats in vivo were all yielded to be one-compartment model.

Administration, Oral ; Animals ; Evodia ; Indole Alkaloids ; pharmacokinetics ; Male ; Plant Extracts ; pharmacokinetics ; Quinazolines ; pharmacokinetics ; Rats ; Rats, Wistar

OBJECTIVETo conduct an experimental study on in vitro transdermal absorption of prepared Shangshi Zhitong cataplasm.

METHODFranz diffusing cells and mice were adopted for the percutaneous penetration study. The accumulative percutaneous permeation of total alkaloids, strychnine and atropine in certain time was determined by acid dye colorimetry and HPLC.

RESULTThe accumulative permeation of alkaloids (Q) increased with time (t), with a linear relation between them.

CONCLUSIONThe in vitro percutaneous penetration of Shangshi Zhitong cataplasm complies with the zero-order kinetics.

Administration, Cutaneous ; Alkaloids ; pharmacokinetics ; Animals ; Atropine ; pharmacokinetics ; Drugs, Chinese Herbal ; pharmacokinetics ; Male ; Mice ; Rats ; Rats, Wistar ; Skin Absorption ; Strychnine ; pharmacokinetics

OBJECTIVETo investigate the regularity of Yulian Cataplasm in vitro release and transdermal behaviors.

METHODImproved Franz diffusion devices was used with four index ingredients as evodiamine, rutaecarpine, palmatine and berberine that were determined by HPLC in one mobile phase.

RESULTThe release rates of evodiamine, rutaecarpine, palmatine and berberine were 0.0239, 0.0156, 0.0725, 0.8191 mg x cm(-2) x h(-1/2), respectivley. The transdermal rates of evodiamine, rutaecarpine, palmatine and berberine were 1.256, 1.0302, 2.8029, 20.919 microg x cm(-2) x h(-1), respectively.

CONCLUSIONThe releasing process of all index is in accordance with Higuchi equation and the transdermal proccess is in accordance with zero-level equation.

Animals ; Berberine ; administration & dosage ; pharmacokinetics ; Berberine Alkaloids ; administration & dosage ; pharmacokinetics ; Drugs, Chinese Herbal ; administration & dosage ; pharmacokinetics ; Indole Alkaloids ; administration & dosage ; pharmacokinetics ; Mice ; Plant Extracts ; administration & dosage ; pharmacokinetics ; Quinazolines ; administration & dosage ; pharmacokinetics ; Skin ; metabolism ; Skin Absorption

A rapid, sensitive, and selective liquid chromatography-tandem mass spectrometry was developed for the simultaneous determination of lycorine and galanthamine, two major constituents in Lycoris radiata extract, in rat plasma. Liquid-liquid extraction with ethyl ether was carried out using diphenhydramine as the internal standard. The two bioactive alkaloids were separated on a Zorbax SB-C18 reserved-phase column (150 mm × 4.6 mm, i.d., 5 μm) by gradient elution using a mobile phase consisting of methanol with 0.1% formic acid (A) and water with 0.1% formic acid (B) at a flow rate of 0.6 mL/min. All analytes showed good linearity over a wide concentration range (r (2)>0.99) and the lower limit of quantification was 3.00 ng/mL for each analyte. The average extraction recovery of the analytes from rat plasma was more than 82.15%, and the intra-day and inter-day accuracy and precision of the assay were less than 12.6%. The validated method was successfully applied to monitoring the concentrations and pharmacokinetic studies of two Amaryllidaceous alkaloids in rat plasma after an oral administration of Lycoris radiata extract.
Amaryllidaceae Alkaloids ; pharmacokinetics ; Animals ; Chromatography, Liquid ; Galantamine ; pharmacokinetics ; Lycoris ; chemistry ; Male ; Parasympathomimetics ; pharmacokinetics ; Phenanthridines ; pharmacokinetics ; Plant Extracts ; chemistry ; pharmacokinetics ; pharmacology ; Rats ; Rats, Wistar ; Tandem Mass Spectrometry ; methods

OBJECTIVETo study the release mechanism of Huperzine-A swelling sustained-release tablets (HA-ST) and the factors influencing the release rate.

METHODThe HA-ST were prepared by using Polyoxyethylene (PEO) as the matrix material, polyvinyl alcohol (PVA) as the expandable reagent and microcrystalline cellulose (MCC) as the filling reagent. The effect of the amount of PEO, PVA and MCC on the drug release from the tablets was evaluated using the release index n value of the Ritger-Peppas equation.

RESULTThe addition of PEO and PVA speeded up the rate of drug release from the tablets, while MCC did not affect the release rate. The release profiles of HA-ST conformed to the Higuchi model and the release mechanism was non-Fick release that coupled diffusion and erosion.

CONCLUSIONThe release of HA-ST is influenced by the amount of PEO and PVA but not the MCC. The release process can be depicted by the Ritger-Peppas equation and release mechanism was is non-Fick release.

Alkaloids ; Cellulose ; chemistry ; Delayed-Action Preparations ; chemistry ; pharmacokinetics ; Diffusion ; Models, Biological ; Polyethylene Glycols ; chemistry ; Sesquiterpenes ; chemistry ; pharmacokinetics ; Tablets ; chemistry ; pharmacokinetics

OBJECTIVETo develop a sensitive and reliable high-performance liquid chromatography-tandem mass spectrometry (LC-MS-MS) method for simultaneous determination of jatrorrhizine, palmatine and berberine in rat serum, and study the pharmacokinetics of the three alkaloids in rat serum after an intragastrical (ig) administration of Huanglianjiedu decoction to rat.

METHODThe optimal ionization and fragmentation conditions, as well as HPLC ones, to detect jatrorrhozine, palmatine and berberine were developed and validated. After the Huanglianjiedu decoction were administered to rats through ig route, LC-MS-MS method has been applied to the pharmacokinetic study of the three alkaloids in rat serum. DAS procedure was used to process concentration-time data.

RESULTThe detection was performed by MRM mode via electrospray ionization (ESI) source operating in the positive ionization mode. The precursor-to-product ion transitions were at m/z 338-322 for jatrorrhozine, m/z 351.9-308 for palmatine, m/z 336-319.8 for berberine and m/z 356.1-192.1 for tetrahydropalmatine (IS) respectively. The method was linear over the concentration range of 0.2-25 microg x L(-1) for jatrorrhozine, 0.4-50 microg x L(-1) for palmatine and berberine. The method was validated according to the requirements. The pharmacokinetic process of the three alkaloids after oral administration of Huanglianjiedu decoction was fitted to be a one-compartment model.

CONCLUSIONThe fully validated LC-MS-MS method has been successfully applied to the pharmacokinetic study of the three alkaloids in rat serum after oral administration of Huanglianjiedu decoction.

Alkaloids ; pharmacokinetics ; Animals ; Berberine ; analogs & derivatives ; pharmacokinetics ; Berberine Alkaloids ; pharmacokinetics ; Chromatography, High Pressure Liquid ; methods ; Drugs, Chinese Herbal ; pharmacokinetics ; Male ; Quality Control ; Rats ; Rats, Sprague-Dawley ; Reference Standards ; Spectrometry, Mass, Electrospray Ionization ; Tandem Mass Spectrometry ; methods

OBJECTIVETo observe the impact on absorption of berberine and palmatine in different compatibilities of Wuji pill by the perfused rat intestine-liver preparation.

METHODUse L9 (3(4)) orthogonal design table, establish the perfused rat intestine-liver preparation, the twelve Wuji pill compatibilities duodenal administrated, collect the perfusate at different times points for LC-MS detection, calculate the absorbed score, Ka.

RESULTEvodiae Fructus and the absorption score, Ka of berberine and palmatine are inverse correlated. The most superior portion which promote the absorption is Coptidis Rhizoma-Evodiae Fructus-Paeoniae Radix Alba 3:1:3.

CONCLUSIONEvodiae Fructus suppressed the absorption of berberine and palmatine. With the different portion the absorption also have big different.

Animals ; Berberine ; metabolism ; pharmacokinetics ; Berberine Alkaloids ; metabolism ; pharmacokinetics ; Drugs, Chinese Herbal ; pharmacology ; Evodia ; chemistry ; Intestinal Absorption ; drug effects ; Male ; Rats

To elucidate the absorption and metabolism of alkaloids in Berberis kansuensis in vivo, a high performance liquid chromatography-triple quadrupole mass spectrometry(HPLC-QqQ-MS) method was developed to qualitatively and quantitatively analyze the absorption components in rat serum in multiple-reaction monitoring mode. The mobile phase consisted of 0.1% formic acid and acetonitrile with a gradient elution mode. In addition, to investigate the effects of gut microbiota on five absorbed components of B. kansuensis in rat serum, diabetic rat and pseudo germ-free diabetic rat models were established, and partial least squares discriminant analysis and One-way ANOVA were used to study the content differences of five components among different groups. In this study, a HPLC-QqQ-MS method for quantitative analysis of five components in rat serum after oral administration of B. kansuensis was established for the first time. It was found that there were differences in the five constituents in rat serum between different groups. By comparing the normal group with the diabetic model group, we found that the absorption and metabolism capacities of berberine and magnoflorine were different under the health and pathological conditions. It was also found that the serum levels of berberine, magnoflorine and jatrorrhizine in pseudo germ-free diabetic rats were significantly lower than those in diabetic rats, indicating that gut microbiota plays an important role in the metabolism of alkaloids of B. kansuensis in vivo. These results provide a good reference for clarifying the active ingredients of B. kansuensis in the treatment of diabetes.
Alkaloids/pharmacokinetics* ; Animals ; Berberis/chemistry* ; Chromatography, High Pressure Liquid ; Diabetes Mellitus, Experimental/blood* ; Gastrointestinal Microbiome ; Mass Spectrometry ; Phytochemicals/pharmacokinetics* ; Rats

The research aimed to evaluate the intestinal absorption of alkaloids extracted by decoction and alcohol extraction proces- ses from Rhizoma Coptidis-Rheum rhabarum herbal pair via everted gut sacs. Berberine, palmatine, coptisine and epiberberine were the main alkaloids in this herbal pair and taken as the standard indexes in the quantitative analysis with multi-components by single marker (QAMS) method, in order to calculate absorption rate constant (Ka) and evaluate intestinal absorption characteristics of these four alkaloids extracted by different extraction methods in different intestinal segments in rats. The results showed that the four alkaloids extracted by two different processes in high, medium and low doses had linear absorption properties in the small intestine segment, which conformed to zero-order absorption rate, intestinal segment than 0.99. The absorption rate constant (Ka) of decoction group was higher than that of alcohol extraction group.
Alkaloids ; pharmacokinetics ; Animals ; Coptis ; chemistry ; Intestinal Absorption ; Male ; Rats ; Rats, Sprague-Dawley ; Rheum ; chemistry