Biomedical subjects

Guang-ji Wang

Publications and source records attributed to Guang-ji Wang.

9 recordsLinked to original sources

PubMed2006

Development and validation of a sensitive quantification method for hematoporphyrin monomethyl ether in plasma using high-performance liquid chromatography with fluorescence detection.

A rapid, sensitive, precise and specific method for determination of hematoporphyrin monomethyl ether (HMME), a novel photodynamic therapy (PDT) drug, was developed and validated using high-performance liquid chromatography (HPLC) with fluorescence detection. HMME was isolated from the plasma by a single-step liquid-liquid extraction with ethyl acetate. The analyte and internal standard fluorescein were baseline separated on a Diamonsil C(18) analytical column (4.6 x 150 mm, 5 microm) and analyzed using a fluorescence detector with the excitation and emission wavelengths set at 395 and 613 nm, respectively. The method was linear in the concentration range 0.025-5 microg/mL with a lower limit of quantitation (LLOQ) of 10 ng/mL. The inter- and intra-day accuracies and precisions were all within 10% and the mean recoveries of HMME and fluorescein were 95 +/- 3.7 and 90 +/- 2.3%, respectively. The analyte was stable during all sample storage, preparation and analysis periods. This method was successfully applied to a pharmacokinetic study after a single-dose intravenous administration of HMME (5 mg/kg) to beagle dogs. This method was reproducible and sensitive enough for the pharmacokinetic study of HMME. Based on the results of the pharmacokinetic study, we suggest that a rather long light-avoiding time is essential for patients under HMME therapy.

Animals↗

PubMed2006

Metabolism and metabolic inhibition of gambogic acid in rat liver microsomes.

AIM: To study the metabolism of gambogic acid (GA) and the effects of selective cytochrome P-450 (CYP450) inhibitors on the metabolism of GA in rat liver microsomes in vitro. METHODS: Rat liver microsomes were used to perform metabolism studies. Various selective CYP450 inhibitors were used to investigate their effects on the metabolism of GA and the principal CYP450 isoform involved in the formation of major metabolite M(1) in rat liver microsomes. Types of inhibition in an enzyme kinetics model were used to model the interaction. RESULTS: GA was rapidly metabolized to two phase I metabolites, M(1) and M(2), in rat liver microsomes. M(1) and M(2) were tentatively presumed to be the hydration metabolite and epoxide metabolite of GA, respectively. alpha-Naphthoflavone uncompetitively inhibited the formation of M(1) while ketoconazole, sulfaphenazole, diethyl dithiocarbamate and quinidine had little or no inhibitory effects on the formation of M(1). CONCLUSION: GA is rapidly metabolized in rat liver microsomes and M(1) is crucial for the elimination of GA. Cytochrome P-450 1A2 is the major rat CYP involved in the metabolism of GA.

Animals↗

PubMed2006

Influence of CYP3A5 genetic polymorphism on cyclosporine A metabolism and elimination in Chinese renal transplant recipients.

AIM: To investigate whether the CYP3A5*3 polymorphism would affect cyclosporine A (CsA) metabolism in Chinese renal transplant patients. METHODS: The CYP3A5*3 genotype was determined in Chinese renal transplant recipients using polymerase chain reaction and amplification of specific alleles (PCR-ASA). The concentrations of CsA and metabolites were separately measured by fluorescence polarization immunoassay and dose-adjusted trough concentrations and metabolic ratio (MR) values were calculated. RESULTS: The trough concentrations adjusted with the dose was significantly higher in the wild allele carriers compared to both the homozygous (*3*3) and heterozygous variants (*1*3). However, no significant difference was found for the dose-adjusted metabolite concentrations. The MR values for the 3 genotype groups were as follows: 0.92+/-0.62 for CYP3A5*3/ *3 (n=14), 0.99+/-0.51 for CYP3A5*1/*3 (n=15), and 1.45+/-0.62 for CYP3A5*1/*1 (n=9), respectively. Post hoc comparisons showed that only the MR values between the CYP3A5*3/*3 group and the CYP3A5*1/*1 group were significantly different. CONCLUSION: The CYP3A5*3 polymorphism exerted little effect on cyclosporine metabolism. The MR may be a more accurate indicator for therapeutic drug monitoring, considering its integrated information on body exposure of both parent drugs and metabolites.

Adult↗

PubMed2006

[In vitro inhibitory effect of 23-HBA on angiogenesis].

AIM: To study the inhibitory effect of 23-HBA on angiogenesis in vitro. METHODS: The effect of 23-hydroxy butulinic acid (23-HBA) on the in vitro proliferation of human microcapillary endothelial cells(HMECs) was examined by sulfonylrhodamine B (SRB) assay. The effect of 23-HBA on endothelial cell migration, and tubule formation on Matrigel was also observed. The CD31 expression in HMECs was dectected by immunohistochemical staining. RESULTS: The proliferation of HMECs was inhibited significantly by 23-HBA with IC(50) being 40.44 mg/L. 23-HBA inhibited endothelial cell migration and tubule formation in a dose-dependent manner. The expression of CD31 in HMECs was reduced after treatment with 10 mg/L 23-HBA. CONCLUSION: 23-HBA can inhibit angiogenesis in vitro, which would become a promising antiangiogenic drug.

Angiogenesis Inhibitors↗

PubMed2005

[Pharmacokinetics of oxymatrine and its metabolite in beagle dogs by LC-MS].

OBJECTIVE: To establish LC-MS method in the determination of oxymatrine and its metabolite in plasma and investigate their pharmacokinetics in beagle dogs. METHOD: Lichrospher C18 column (4.6 mm x 250 mm, 5 microm) was used as the analytical column maintained at 25 degrees C. The mobile phase consisted of 10 mmol x L(-1) CH3COONH4 and CH3OH (25:75). Flow rate was 1 mL x min(-1). Electrospray ionization (ESI) was carried out. The ESI ion source was set in positive ion polasity mode. The selective ion monitoring (SIM) was set at m/z 265.1 and 249.2. RESULT: The linearity ranged from 2 to 5000 ng x mL(-1) (r = 0.9991). The detection of oxymatrine and its metabolite were 0.6 and 0.3 ng x mL(-1). The RSD(%) within day and between day was less than 4.7%. The recovery of this method was more than 96.5%. The disposition was conformed to a two-compartment model. The T(1/2), Tmax, Cmax, MRT, AUC(0-->24 h) of oxymatrine were (5.5+/-1.58) h, (1.0+/-0.30) h, (2418.3 +/-970.78) ng x mL(-1), (3.2+/-0.64) h, (5797.4+/-908.16) ng x mL(-1) x h accordingly. The corresponding T(1/2), Tmax, Cmax, MRT, AUC(0-->24 h) of matrine were (9.8+/-2.77) h, (1.9+/-1.09) h, (1532.4+/-494.86) ng x mL(-1), (4.4+/-1.97) h, (5530.5+/-1042.65) ng x mL(-1) x h. CONCLUSION: This assay was highly sensitive, rapid, simple and specific enough for determining concentrations of oxymatrine and its metabolite matrine in plasma of beagle dog.

Administration, Oral↗

PubMed2003

[Inhibitory action of berberine on glucose absorption].

AIM: To study the absorption characteristics of berberine and its influence on glucose absorption. METHODS: Rat recirculating perfusion model was used to study berberine absorption characteristics and Caco-2 cell model was used to explore the influence of berberine on disaccharidase, using HPLC to assay the appearance of glucose to indicate enzyme activities. RESULTS: Berberine was found to be hardly absorbed in the intestine (less than 5% in 2.5 h). However, sucrase and maltase activities were found to be inhibited by berberine, its ID50 to sucrase is 1.830 mg.L-1, and showed no dose dependent influence on maltase activity. Berberine also showed influence on glucose absorption. However, this effect is not significant. CONCLUSION: Berberine may act as an alpha-glucosidase inhibitor, which is its main mechanism in diabetes treatment.

Animals↗

PubMed2002

[Study on the metabolites of guanfu base A hydrochloride in rat urine by high performance liquid chromatograph-mass spectrum].

AIM: To study the metabolites of guanfu base A hydrochloride (GFA) in rat urine. METHODS: Rat urine was collected after i.v. injection of GFA. Phase I metabolites were identified by HPLC/MS and by comparison with authentic standards. Phase II conjugates were treated with either glucuronidase or sulfatase in presence or absence of glucuronidase specific inhibitor D-saccharic acid beta-1,4-lactone. The aglycones were identified by HPLC/MS. RESULTS: Phase I metabolites guanfu base I (GFI) and guanfu alcohol-amine (AA) were separated and identified in rat urine by comparison with authentic standards. Phase II conjugates, for which no authentic standards were available, GFA glucuronide and sulfate conjugates, GFI glucuronide and sulfate were separated and tentatively identified by hydrolysis with glucuronidase or sulfatase, the aglycones, GFA and GFI, were identified in rat urine. CONCLUSION: After i.v. injection of GFA, GFA is metabolized into GFI, AA, GFA glucuronide and sulfate conjugates, GFI glucuronide and sulfate conjugates in rat urine. The polarity of the metabolites is increased, and the effectiveness of them is lower than the parent drug.

Aconitum↗

PubMed2002

[HPLC determination of insulin and its related substances in insulin powder for inhalation].

AIM: To determine insulin and its related substances in insulin powder for inhalation by reversed phase high performance liquid chromatography method. METHODS: The initial mobile phase was solution A (0.1% trifluoroacetic acid-acetonitril 70:30) and changed to solution B (0.1% trifluoroacetic acid-acetonitril 60:40) in 30 minutes. The flow rate was 2.0 mL.min-1, the column temperature was 30 degrees C, the wave length was 280 nm, the injected volume was 20 microL. RESULTS: Insulin was well separated from other peaks induced in different conditions. There was good linear relationship between the amount of insulin and its peak area, the RSD was 1.1%, the insulin solution for determination was stable in 12 hours, and the quantity detected was near the added. CONCLUSION: The method is simple and accurate to detect insulin and its related substances in insulin and its preparations.

Administration, Inhalation↗

PubMed2002

[Determination of guanfu base A hydrochloride in plasma by LC-MS method and its pharmacokinetics in dogs].

AIM: To establish an analytical method for determination of guanfu base A (GFA) concentration in plasma and to study its pharmacokinetic profile in dogs. METHODS: Six dogs were given a 7.56 mg.kg-1 dose intravenously. Blood samples were collected at various time-points after drug administration. Analytical method based on liquid chromatography-mass spectrometry (LC-MS) was established to determine the plasma concentration of GFA. Pharmacokinetic evaluation was carried out using the 3P87 program. RESULTS: The calibration curves were linear over the concentration range from 0.42 microgram.mL-1 to 21.2 micrograms.mL-1 (gamma = 0.9994). The intra-day and inter-day precisions were generally good (< 15%) at low, medium and high concentrations. The overall recovery of the analytes was more than 80%. Six dogs were given an i.v. dose of 7.56 mg.kg-1 of GFA hydrochloride, an open three compartment model best described the concentration-time profiles for GFA. The half-lives for the rapid and slow distribution phase and terminal elimination phase (T1/2 pi, T1/2 alpha and T1/2 beta) were 0.07 h, 1.5 h, and 13.5 h, respectively. The total area under the plasma concentration-time curve (AUC), the volume of the central compartment (Vc), and plasma clearance (CLs) were 61.43 micrograms.h.mL-1, 0.37 L.kg-1 and 0.14 L.kg-1.h-1, respectively. CONCLUSION: The analytical method was shown to be sensitive, specific, rapid and reproducible, and was suitable for pharmacokinetic studies of GFA.

Aconitum↗