An RP-HPLC was established to determine scutellarin in rabbit plasma and to study pharmacokinetics of breviscapine in rabbits. The analytical column was DiamonsilTM C18(4.6 mm x 250 mm, 5 microns), the mobile phase consisted of methanol, 0.02 mol/L phosphate buffer(adjusted by phosphoric acid to pH 3.0) and acetonitrile (65:35:10), the flow rate was 1.0 ml.min-1, the column temperature was 25 degrees C and the detection wavelength was 334 nm. The results of the pharmacokinetics study showed that the concentration-time curve of scutellarin was conformed to two-compartment model, the chief pharmacokinetic parameters were as follows: t1/2 alpha 1.29 +/- 0.53 min, t1/2 beta 10.40 +/- 1.97 min, Vc148.1 +/- 118.6 ml, and CL 57.5 +/- 31.7 ml.min-1.
Animals ; Apigenin ; Chromatography, High Pressure Liquid ; methods ; Female ; Flavonoids ; administration & dosage ; blood ; pharmacokinetics ; Glucuronates ; blood ; Injections, Intravenous ; Male ; Rabbits

OBJECTIVE: To develop a method for determining ethyl glucuronide(EtG) in human blood with gas chromatograph-tandem mass spectrometry (GC-MS/MS). METHODS: Human blood protein was precipitated with acetonitrile. The supernatant was transferred and air flow dried after centrifugated. The residue was derived with N, O-bis (trimethylsilyl)trifluoroacetamide (BSTFA), and analyzed with GC-MS/MS. RESULTS: The detection limit of EtG in blood was 0.05 microg/mL. Calibration curve covered a span from 0.1-10 microg/mL with a good linear relationship (r = 0.999 9). The method showed a excellent performance when was used to authentic blood sample analysis for EtG. CONCLUSION The method is suitable for blood EtG analysis.
Alcohol Drinking/blood* ; Alcoholism/blood* ; Biomarkers/blood* ; Forensic Toxicology/methods* ; Gas Chromatography-Mass Spectrometry/methods* ; Glucuronates/blood* ; Humans ; Reproducibility of Results ; Sensitivity and Specificity

OBJECTIVEA HPLC-ECD method was established to determine scutellarin in rat bile.

METHODThe analytical column was Prontosil C18 (4.6 mm x 250 mm, 5 microm), and the mobile phase was consisted of methanol, 50 mmol x L(-1) phosphate buffer (adjusted by phosphoric acid to pH 2. 6), and tetrahydrofuran (40: 60: 10) , the flow rate was 1.0 mL x min(-1); the potential electrode voltage was 100 mv.

RESULTConcentration profile of scutellarin in rat bile was shown in this paper after oral administration of scutellarein.

CONCLUSIONOnly scutellarin was detected in rat bile, while both of scutellarin and scutellarein were detected in rat plasma.

Animals ; Apigenin ; analysis ; blood ; isolation & purification ; Bile ; chemistry ; Chromatography, High Pressure Liquid ; Erigeron ; chemistry ; Glucuronates ; analysis ; Male ; Plants, Medicinal ; chemistry ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo establish a UPLC-MS/MS analysical method for simultaneous determination of concentrations of isoorientin, scutellarin and cynaroside in rat plasma and to study their pharmacokinetic characteristics after intravenous injection of 3 doses of Fufang Hongcao in rats.

METHODAcidified plasma samples were precipitated for protein with methanol. Waters Acquity BEH C18 column was adopted for spectrum, with mobile phase as 0. 1% formic acid acetonitrile-0. 1% formic acid-water gradient elution. Detection was carried out by the multiple reaction monitoring (MRM) positive ion mode with ESI ionization source.

RESULTThree flavonoids show a good linear relationship, with the extraction recovery ranging between 78.56% and 101.91% and a high intra-and inter-day precisions and accuracy. The MRT of the three flavonoids were all lower than 22 min in rats.

CONCLUSIONThe above men tioned method is so specific, rapid, sensitive that it is suitable for pharmacokinetic studies of Fufang Hongcao injection in rats.

Animals ; Apigenin ; blood ; pharmacokinetics ; Chromatography, High Pressure Liquid ; methods ; Drugs, Chinese Herbal ; pharmacokinetics ; Female ; Glucosides ; blood ; pharmacokinetics ; Glucuronates ; blood ; pharmacokinetics ; Luteolin ; blood ; pharmacokinetics ; Male ; Rats ; Tandem Mass Spectrometry ; methods ; Time Factors

OBJECTIVETo investigate the pharmacokinetic and distribution character of scutellarin in plasma and tissues in rats, in order to provide some references for rational drug use in the clinic.

METHODThe solution of scutellarin was administered to rats (80 mg x kg(-1)) by oral gavage. A high performance liquid chromatography method determinated the scutellarin concentration in rat plasma and tissue. The plasma samples were performed by solid phase extraction method. The other biological samples were extracted by ethyl acetate.

RESULTThe range of scutellarin in plasma and tissue in rats were 10-1280 ng x mL(-1) (R2 > 0.99), 40-1280 ng x g(-1) (R2 > 0.99), respectively. The lowest detection of scutellarin were 10 ng x mL(-1) and 40 ng x g(-1), the precision were less than 8%. The main pharmacokinetic parameters of scutellarin were as follows: tmax, Cmax, AUC and MRT being (7.7 +/- 0.9) h, (288.0 +/- 75.2) microg x L(-1), (5.6 +/- 1.6) microg x mL(-1) x h(-1), (17.5 +/- 1.4) h(-1), respectively.

CONCLUSIONThese methods applied the study of pharmacokinetics of scutellarin. After oral the scutellarin in rats, the concentration-time course doesn't obey any compartment model. The concentration-time curve is the double peaks.

Animals ; Apigenin ; blood ; isolation & purification ; pharmacokinetics ; Area Under Curve ; Chromatography, High Pressure Liquid ; Female ; Glucuronates ; blood ; isolation & purification ; pharmacokinetics ; Male ; Plants, Medicinal ; chemistry ; Rats ; Rats, Sprague-Dawley ; Tissue Distribution

AIMTo prepare the breviscapine liposomes and study the pharmacokinetics of breviscapine liposomes in Beagle dogs.

METHODSThe cross-over design (two periods) was employed. Six Beagle dogs were administrated a single intravenous dosage of 28 mg of breviscapine liposomes and reference preparation, respectively, scutellarin in plasma of 6 dogs at different sampling time was determined by RP-HPLC. The pharmacokinetic parameters were calculated by 3P97 program and compared by statistic analysis.

RESULTSThe mean concentration-time curves of breviscapine liposomes and reference preparation were both fitted to two-compartment model with the main pharmacokinetic parameters as follows: T 1/2 alpha were (4.4 +/- 0.7) min and (1.8 +/- 1.3) min respectively; T 1/2 beta were (55 +/- 27) min and (28 +/- 23) min respectively; V(c) were (1 580 +/- 265) mL and (2 460 +/- 2 200) mL respectively; CL(s) were (88 +/- 10) mL x min(-1) and (324 +/- 69) mL x min(-1) respectively; and AUC(0-720) were (363 +/- 42) microg x min x mL(-1) and (102 +/- 19) microg x min x mL(-1) respectively. The T 1/2 alpha, CL(s) and AUC(0-720) of breviscapine liposomes all had significant difference from those of reference preparation, after the data were examined by a one-way analysis of variance (ANOVA).

CONCLUSIONCompared with the reference preparation, breviscapine liposomes had a much more higher concentration in plasma and contained characteristic of sustained-release, which ameliorated the pharmacokinetic properties of scutellarin.

Animals ; Apigenin ; blood ; Area Under Curve ; Brain ; metabolism ; Cross-Over Studies ; Delayed-Action Preparations ; Dogs ; Drug Compounding ; Drug Stability ; Erigeron ; chemistry ; Female ; Flavonoids ; administration & dosage ; isolation & purification ; pharmacokinetics ; Glucuronates ; blood ; Injections, Intravenous ; Liposomes ; Male ; Plants, Medicinal ; chemistry

Scutellarin is the main effective constituent of breviscapine, a flavonoid mixture isolated from the dried whole plant of Erigeron breviscapus (Vant.) Hand-Mazz, and valsartan is used as an antihypertensive drug. These two drugs have already been clinically used together to treat diabetic nephropathy (DN) in China, and the combined medications showed some enhanced protection against DN. The aim of this study is to investigate the potential pharmacokinetic interaction between scutellarin and valsartan in rats. Breviscapine injection (20 mg x kg(-1), i.v.) and valsartan (15 mg x kg-, i.g.), either alone or together were given to 18 male Sprague-Dawley rats. Concentrations of scutellarin and valsartan were quantified by HPLC, and pharmacokinetic parameters were calculated by non-compartmental methods. We found that the pharmacokinetic parameters of scutellarin altered significantly after co-administration of oral valsartan. The plasma clearance (CL(p)) and the bile clearance (CL(b)) of scutellarin were reduced significantly in the presence of valsartan. After oral administration of valsartan with or without intravenous scutellarin, however, the pharmacokinetic parameters of valsartan were comparable. In conclusion, our data suggests that the concurrent use of valsartan reduces the biliary excretion of scutellarin, and this may be due to the inhibitory effect of valsartan on the biliary excretion of scutellarin mediated by Mrp2 (Multidrug resistance-associated protein 2).
Administration, Intravenous ; Administration, Oral ; Animals ; Antihypertensive Agents ; administration & dosage ; blood ; pharmacokinetics ; Apigenin ; administration & dosage ; blood ; isolation & purification ; pharmacokinetics ; Bile ; metabolism ; Chromatography, High Pressure Liquid ; Drug Interactions ; Erigeron ; chemistry ; Glucuronates ; administration & dosage ; blood ; isolation & purification ; pharmacokinetics ; Male ; Metabolic Clearance Rate ; Multidrug Resistance-Associated Proteins ; metabolism ; Plants, Medicinal ; chemistry ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Valsartan ; administration & dosage ; blood ; pharmacokinetics

This study is to investigate the transportation of scutellarin in cell and live models and study on mechanism of absorption and transport of scutellarin in mouse liver. The concentration of scutellarin in plasma and liver from control and pretreated groups was determined by high performance liquid chromatography. The uptake of scutellarin was examined in control hepatocytes group, induced hepatocytes group and induced hepatocytes plus pravastatin group. Pravastatin can affect the pharmacokinetics of scutellarin in mouse: CL is decreased while AUC is increased. The scutellarin absorption of hepatocyte induced group was higher than that of control group, but was decreased in the group with pravastatin added. The research showed that there was potential drug interaction between pravastatin and scutellarin. The drugs may compete for oatp2 mediated transport pathway consisted in the uptake of scutellarin in liver.
Absorption ; Animals ; Apigenin ; blood ; metabolism ; pharmacokinetics ; Area Under Curve ; Biological Transport ; Cell Survival ; Chromatography, High Pressure Liquid ; methods ; Drug Interactions ; Glucuronates ; blood ; metabolism ; pharmacokinetics ; Hepatocytes ; cytology ; metabolism ; Liver ; metabolism ; Male ; Mice ; Organic Cation Transport Proteins ; metabolism ; Pravastatin ; metabolism ; pharmacology ; Pregnenolone Carbonitrile ; pharmacology ; Random Allocation

AIMTo determine scutellarin in dog plasma and study the pharmacokinetics of scutellarin in the dog.

METHODSScutellarin in plasma of six dogs at different sampling time was determined after single dose of 120 mg i.v. by RP-HPLC. The mean plasma concentration-time curve was protracted and pharmacokinetic parameters were calculated.

RESULTSThe concentration-time curve of scutellarin can be fitted to a three-compartment model with the main pharmacokinetic parameters as follows: T1/2 gamma, T1/2 alpha and T1/2 beta were (1.1 +/- 0.8) min, (7.0 +/- 2.8) min and (52 +/- 29) min, respectively, Vc was (880 +/- 508) mL, CL was (190 +/- 54) mL.min-1, AUC0-90 and AUC0-infinity were (574 +/- 134) mg.min.L-1 and (559 +/- 132) mg.min.L-1 respectively.

CONCLUSIONThe concentration of scutellarin in plasma declined rapidly after single dose of 120 mg i.v. in dogs, and this suggested that the T1/2 of scutellarin should be taken into account in preparation exploitation and drug administration.

Animals ; Apigenin ; Area Under Curve ; Asteraceae ; chemistry ; Chromatography, High Pressure Liquid ; Dogs ; Drugs, Chinese Herbal ; administration & dosage ; isolation & purification ; pharmacokinetics ; Female ; Flavonoids ; blood ; isolation & purification ; pharmacokinetics ; Glucuronates ; blood ; isolation & purification ; pharmacokinetics ; Injections, Intravenous ; Male ; Plants, Medicinal ; chemistry ; Vasodilator Agents ; administration & dosage ; pharmacokinetics

Double cannulation model of conscious rat allowing simultaneous collection of mesenteric lymph and jugular venous blood was established to investigate the intestinal lymphatic transport of breviscapine orally administered in rat. The concentrations of breviscapine in plasma and lymph were determined by HPLC. The pharmacokinetics of breviscapine after oral and intravenous administration was evaluated in the conscious rat model. It was observed that scutellarin distributed from blood circulation to lymphatic system after intravenous injection. The cumulative lymphatic transport amount within 12 h was (2.78 +/- 0.25) microg, equivalent to 0.0792% of intravenous dose. After oral administration of scutellarin to double-cannulation rats, the cumulative lymphatic transport amount within 12 h was (0.92 +/- 0.08) microg, equal to 0.0083% of oral dose. The absolute bioavailability of breviscapine orally administered to double-cannulation rats was 4.91%, indicating that scutellarin was mainly absorbed into the bloodstream through the portal vein. Lymphatic transport of scutellarin appears to reflect high affinity for the lymph lipoproteins to chylomicron. This study provided a biopharmaceutics basis for developing oral lipid delivery system for the promotion of intestinal lymphatic transport to improve oral bioavailability of breviscapine.
Administration, Oral ; Animals ; Apigenin ; blood ; metabolism ; Area Under Curve ; Biological Availability ; Biological Transport ; Drug Delivery Systems ; methods ; Flavonoids ; administration & dosage ; isolation & purification ; pharmacokinetics ; Glucuronates ; blood ; metabolism ; Injections, Intravenous ; Intestinal Absorption ; Lymphatic System ; metabolism ; Male ; Plants, Medicinal ; chemistry ; Portal Vein ; metabolism ; Rats ; Rats, Sprague-Dawley