Biomedical subjects

Guang-Ji Wang

Publications and source records attributed to Guang-Ji Wang.

At least 19 recordsLinked to original sources

PubMed2007

Determination of gambogic acid in dog plasma by high-performance liquid chromatography for a pharmacokinetic study.

A rapid, simple and sensitive high-performance liquid chromatography method for the quantification of gambogic acid in dog plasma was developed and validated. After acidification with hydrochloric acid, dog plasma was extracted with ethyl acetate and determined by HPLC. The analysis was carried out on a reversed-phase C(18) analytical column. The mobile phase consisted of a mixture of methanol-0.05% phosphoric acid (94:6, v/v), and the column temperature was maintained at 35 degrees C. A constant mobile phase flow rate of 1.0 mL/min was employed throughout the analyses. The ultraviolet detector was set at 360 nm. Chromatographic separation was achieved in less than 10 min and the calibration curve was linear over a concentration range of 0.156-20 microg/mL. The intra-assay and inter-assay variability values were less than 10.0%. The accuracy ranged from 93.0 to 104.2%. The established method has been successfully applied to a pharmacokinetic study of gambogic acid in dogs.

Animals↗

PubMed2007

CYP3A4 mediated in vitro metabolism of vinflunine in human liver microsomes.

AIM: To study the metabolism of vinflunine and the effects of selective cytochrome P-450 (CYP450) inhibitors on the metabolism of vinflunine in human liver microsomes. METHODS: Individual selective CYP450 inhibitors were used to investigate their effects on the metabolism of vinflunine and the principal CYP450 isoform involved in the formation of metabolites M(1) and M(2) in human liver microsomes. RESULTS: Vinflunine was rapidly metabolized to 2 metabolites: M(1) and M(2) in human liver microsomes. M(1) and M(2) were tentatively presumed to be the N-oxide metabolite or hydroxylated metabolite and epoxide metabolite of vinflunine, respectively. Ketoconazole uncompetitively inhibited the formation of M(1), and competitively inhibited the formation of M(2), while alpha-naphthoflavone, sulfaphenazole, diethyl dithiocarbamate, tranylcypromine and quinidine had little or no inhibitory effect on the formation of M(1) and M(2). CONCLUSION: Vinflunine is rapidly metabolized in human liver microsomes, and CYP3A4 is the major human CYP450 involved in the metabolism of vinflunine.

Aryl Hydrocarbon Hydroxylases↗

PubMed2007

Pharmacokinetics of the ginkgo B following intravenous administration of ginkgo B emulsion in rats.

Ginkgo B (GB) is an extract from the leaves of Ginkgo biloba, used in the treatment of dementia, cerebral insufficiency or related cognitive decline. In this paper, the main features of the pharmacokinetics of GB emulsion in rats were reviewed and the binding rate of GB to rat plasma and human plasma protein were investigated meanwhile. The concentrations of GB in plasma, tissue, and excretion of rats after i.v. administration of GB were measured using HPLC-ESI-MS. The metabolite was qualitated by LC-MS/MS. Intravenously administered GB was eliminated in a biphasic manner with a prominent initial phase (half-life of 0.3 h) followed by a slower terminal phase (half-life of 1.5 h). After i.v. 4, 12 and 36 mg/kg GB emulsion, the pharmacokinetic parameters from a two compartment model analysis of plasma samples were AUC(0-tau) (microg x min/ml): 53.7, 165.5 and 649.7; CL (l/min/kg): 0.07, 0.07 and 0.05; V(C) (l/kg): 2.27, 3.27 and 2.76, respectively. Peak concentrations generally occurred at 10 min except brain and fat. Tissue concentration then declined by several-fold during 6 h although still present in most tissues at 6 h. Single intravenous dose was mainly excreted in the urine (40-50%), feces contained less than 30%. The binding rate to rat plasma was little higher than to human plasma, but the difference was negligible. Some metabolites were found in urine and bile through qualitative analysis on the urine and bile by LC-MS/MS.

Animals↗

PubMed2006

Warfarin maintenance dose adjustment with indirect pharmacodynamic model in rats.

The purpose of the study was to adjust the individual maintenance dose of warfarin with a simple approach based on indirect pharmacodynamic model (IDR). Based on the distinct pharmacokinetic and pharmacodynamic features of warfarin, the relationship between the maintenance dose and the steady-state anticoagulation effect was simplified and an approach for the maintenance dose adjustment was proposed. According to the steady-state anticoagulation effect before and after multiple doses (0.1 mg kg(-1)day(-1)), the optimal maintenance doses were predicted for the target anticoagulation effect (INR(target)=2.5), then the actual anticoagulation effect (prothrombin times, PT) on the 6th (8 pm)\8th (8 am)\10th (2 pm) day after dose adjustment according the present method was compared with the target effects with a view of determination the feasibility and accuracy of the proposed approach. The proposed method was also used to adjust warfarin maintenance doses in the presence of metabolism inhibitor metronidazole. The results suggested that the proposed approach could appropriately achieve the target international normalized ratio (INR(target)) when warfarin used alone or in combination with metronidazole, the actual INR values of three days were 2.69+/-0.18 and 2.52+/-0.22 (mean+/-S.D.), respectively. The method provided a relatively simple and accurate strategy for warfarin maintenance dose adjustment.

Administration, Oral↗

PubMed2006

Quantitative determination of ginsenoside Rh2 in rat biosamples by liquid chromatography electrospray ionization mass spectrometry.

Ginsenoside Rh2 is a "hot" natural compound with great potential as a new anti-cancer drug based on abundant pharmacological experiments. However, no systemic pharmacokinetic study of Rh2 was reported because current analysis methods could not fully meet the requirements. Thus, we developed a simple LC/MS method with highly improved sensitivities for the determination of Rh2 in rat plasma, bile, urine, feces and most tissues. The tissues and feces were firstly homogenized mechanically using buffer and methanol as the media, respectively. Plasma, bile, urine and tissue homogenates were extracted with diethyl ether for sample preparation. Feces homogenates were directly deproteinized with acetonitrile. The subsequent analysis procedures were performed on a Shimadzu LCMS2010A system (electrospray ionization single quadrupole mass analyzer), with an ODS column (150 mm x 2.0-mm i.d., 5 microm) plus a C18 guard column for separation and ammonium chloride (500 micromol) as mobile phase additive. The proportions of mobile phase were changed timely according to gradient programs. Chlorinated adducts of molecular ions [M + Cl]- of Rh2 at m/z 657.35 and internal standard digitoxin at m/z 799.55 were monitored in selective ion monitoring mode of negative ions. The method was validated to be accurate, precise and rugged with good linearity in all matrices, according to the FDA guidelines. The lower limits of quantitation in rat plasma, urine and feces were 0.2, 0.2 and 20 ng/mL respectively. Stability studies were also performed, indicating that there were no stability-related problems in the analytical procedure of Rh2. The proposed method was successfully applied to the preclinical pharmacokinetic research of Rh2 in rats, including plasma kinetics, tissue distribution and excretion studies.

Animals↗

PubMed2006

Simple, sensitive and rapid LC-MS method for the quantitation of indapamide in human plasma--application to pharmacokinetic studies.

A sensitive and specific method using liquid chromatography with electrospray ionization mass spectrometry (LC-ESI-MS) has been developed and validated for the identification and quantification of indapamide in human plasma. A simple liquid-liquid extraction procedure was followed by injection of the extracts on to a C18 column with gradient elution and detection using a single quadrupole mass spectrometer in selected ion monitoring (SIM) mode. The method was tested using six different plasma batches. Linearity was established for the concentration range 0.5-100.0 ng/ml, with a coefficient of determination (r) of 0.9998 and good back-calculated accuracy and precision. The intra- and inter-day precision (RSD%) was lower than 10%, and accuracy ranged from 85 to 115%. The lower limit of quantification was reproducible at 0.2 ng/ml with 0.2 ml plasma. The proposed method enables the unambiguous identification and quantification of indapamide for pre-clinical and clinical studies.

Antihypertensive Agents↗

PubMed2006

Identification of tanshinone IIA metabolites in rat liver microsomes by liquid chromatography-tandem mass spectrometry.

Tanshinone IIA, the major component extracted from Radix salvia miltiorrhiza, has been observed to possess various kinds of pharmacological activities including antioxidant, prevention of angina pectoris and myocardial infarction and anticancer. Tanshinone IIA was incubated with rat liver microsomes and the resulting metabolites were identified by liquid chromatography/tandem mass spectrometry. The results showed the formation of three main hydroxyl metabolites. The three hydroxyl metabolites of tanshinone IIA were proved to be tanshinone IIB, hydroxytanshinone IIA and przewaquinone A by comparing the tandem mass spectra and the chromatographic retention time with that of the respective authentic compounds. Tanshinone IIB, hydroxytanshinone IIA and przewaquinone A are all the chemical components of total tanshinones. It was reasonable to presume that the three hydroxy metabolites of tanshinone IIA were pharmacologically active the same as tanshinone IIA and the total tanshinones.

Abietanes↗

PubMed2006

Characterization of metabolites of tanshinone IIA in rats by liquid chromatography/tandem mass spectrometry.

The metabolism of tanshinone IIA was studied in rats after a single-dose intravenous administration. In the present study, 12 metabolites of tanshinone IIA were identified in rat bile, urine and feces with two LC gradients using LC-MS/MS. Seven phase I metabolites and five phase II metabolites of tanshinone IIA were characterized and their molecular structures proposed on the basis of the characteristics of their precursor ions, product ions and chromatographic retention time. The seven phase I metabolites were formed, through two main metabolic routes, which were hydroxylation and dehydrogenation metabolism. M1, M4, M5 and M6 were supposedly tanshinone IIB, hydroxytanshinone IIA, przewaquinone A and dehydrotanshinone IIA, respectively, by comparing their HPLC retention times and mass spectral patterns with those of the standard compounds. The five phase II metabolites identified in this research were all glucuronide conjugates, all of which showed a neutral loss of 176 Da. M9 and M12 were more abundant than other identified metabolites in the bile, which was the main excretion path of tanshinone IIA and the metabolites. M12 was the main metabolite of tanshinone IIA. M9 and M12 were proposed to be the glucuronide conjugates of two different semiquinones and these semiquinones were the hydrogenation products of dehydrotanshinone IIA and tanshinone IIA, respectively. This hydrogenized reaction may be catalyzed by the NAD(P)H: quinone acceptor oxidoreductase (NQO). The biotransformation pathways of tanshinone IIA were proposed on the basis of this research.

Abietanes↗

PubMed2006

Simple, sensitive and rapid liquid chromatography/atmospheric pressure chemical ionization mass spectrometric method for the quantitation of Ranolazine in rat plasma.

A sensitive and specific method using liquid chromatography with atmospheric pressure chemical ionization mass spectrometry (LC/APCI-MS) has been developed and validated for the identification and quantification of Ranolazine in rat plasma. A simple liquid-liquid extraction procedure was followed by injection of the extracts onto a C18 column with isocratic elution and detection using a single quadrupole mass spectrometer in selected ion monitoring (SIM) mode. The method was tested using six different batches of blank plasma. Linearity was established for the concentration range 0.02-10.0 microg/mL, with a coefficient of determination (r) of 0.9998 and good back-calculated accuracy and precision. The intra- and inter-day precision (relative standard deviation (RSD) %) was lower than 10%, and accuracy ranged from 85 to 115%. The lower limit of quantification was reproducible at 0.01 microg/mL with 20 microL plasma. The proposed method enables the unambiguous identification and quantification of Ranolazine for pre-clinical and clinical studies.

Acetanilides↗

PubMed2006

Simultaneous determination of tanshinone IIA and its three hydroxylated metabolites by liquid chromatography/tandem mass spectrometry.

A rapid and sensitive method based on liquid chromatography/tandem mass spectrometry (LC/MS/MS) for the simultaneous determination of tanshinone IIA and its three hydroxylated metabolites, tanshinone IIB, hydroxytanshinone IIA and przewaquinone A, in a rat liver microsome was developed and fully validated. A single step of liquid-liquid extraction with ethyl acetate was utilized in this method. Chromatographic separation of the sample matrix from the analytes and the internal standard diazepam was performed using a Shim-pack VP-ODS analytical column. Detection was performed on a triple quadrupole tandem mass spectrometer equipped with an electrospray ionization source and operated in selected reaction monitoring (SRM) mode. The method was linear in the concentration range of 1-500 ng/mL for all analytes. The intra- and inter-day precisions (RSD %) were within 15% and deviations of the assay accuracies were within 15.0% for all analytes. The analytes proved to be stable during sample storage, preparation and analyses. This validated method was successfully applied to the enzyme kinetic study of tanshinone IIA in liver microsome. The elimination of tanshinone IIA and formation of tanshinone IIB and hydroxytanshinone IIA in the liver microsome all exhibited a sigmoidal kinetics profile. The formation of przewaquinone A shows a typical hyperbolic profile. In addition, this method has now been applied in the analysis of other bio-samples including plasma, urine, bile and feces.

Abietanes↗

PubMed2006

Principles and designs of the iseikonic lenses for near vision.

PURPOSE: The purposes of this study were to find the problems of afocal iseikonic lenses as used for near vision and to elaborate the principles and designs of the ideal near iseikonic lenses. METHODS: By analyzing the image-object relationship and imaging processes, the formulae were derived to quantitatively and qualitatively describe two errors of afocal iseikonic lenses as used for near vision: 1) inequality of accommodative demands to both eyes and 2) the difference between the actual and the nominal magnification. Formulae were derived to calculate and design the ideal near iseikonic lenses. RESULTS: For iseikonic lenses now used for near vision, inequality of accommodative demands to both eyes and difference between the actual and nominal magnification increased as the magnification increased and the viewing distance decreased. Afocal iseikonic lenses have significant inequality of accommodative demands to both eyes with 3% magnification at a viewing distance of 25 cm or with 5% magnification at 40 cm. The ideal near iseikonic lenses were found to be flatter than the afocal ones. A series of the ideal near iseikonic lenses were designed with some practical considerations. The central thickness and the refractive index of the lenses affect magnification and lens shape. The thicker the lenses, the higher the magnification. The higher refractive index also gives higher magnification. CONCLUSIONS: Iseikonic lens design is much different for distance and near vision. When the iseikonic lenses are used at a distance other than the designated distance, they will cause blurred vision and artificial aniseikonia as a result of inequality of accommodative demands to both eyes. In research as well as clinical settings, it is necessary to apply the ideal near iseikonic lenses for near vision.

Accommodation, Ocular↗

PubMed2006

Gene variants in noncoding regions and their possible consequences.

Human biodiversity or individual traits are not well explained by exonic mutations of all 20,000 known human genes. Accumulating evidence has demonstrated that not all noncoding regions are junk DNA sequences, and that some functionally important noncoding variants contribute significantly to altered gene expression, qualitatively or quantitatively. Thus, functional profiling or clinical relevance of noncoding variations should not be underestimated or ignored. To validate these concepts, some important examples are discussed further in this short review.

5' Untranslated Regions↗

PubMed2006

[Fluorescence characteristic of terbium-ciprofloxacin complex and its application].

On binding to deoxyribonucleic acid, the complex of terbium-ciprofloxacin (Tb(3+)-CIP) increases its fluorescence quantum efficiency. Based on this, an easy, rapid and sensitive method for the determination of DNA was developed. Like ethidium bromide (EB), the complex can be intercalated into DNA bases, but it is non-poisonous. Determination can be made at pH 7.0, where the native structure of DNA is not disrupted. The maximum emission is at 545 nm with excitation at 325 nm. This method has good sensitivity (2.8 x 10(-9) mol x L(-1) of ctDNA), high selectivity and a wide linear range (4.3 x 10(-7)-3. 0 x 10(-5) mol x L(-1) of ctDNA). This complex was also employed for the clinical examination of DNA in whole blood of tumor patients. Ten tumor patients and 10 normal persons were enrolled in this study. It was showed that significant difference existed between control group and tumor group (p < 0.05).

Animals↗

PubMed2005

Simple, sensitive and rapid LC-ESI-MS method for the quantitation of lafutidine in human plasma--application to pharmacokinetic studies.

A sensitive and specific liquid chromatography electrospray ionization mass spectrometry (LC-ESI-MS) method has been developed and validated for the identification and quantification of lafutidine in human plasma. Lafutidine and internal standard were isolated from plasma samples by liquid-liquid extraction with diethyl ether. The chromatographic separation was accomplished on a stainless-steel column (C18 Shim-pack 5 microm 150 mm x 2.0 mm i.d. Shimadzu) at a flow rate of 0.2 ml/min by a gradient elution. Detection was performed on a single quadrupole mass spectrometer by selected ion monitoring (SIM) mode via electrospray ionization (ESI) source. The method was proved to be sensitive and specific by testing six different plasma batches. Linearity was established for the range of concentrations 1.0-400.0 ng/ml with a coefficient of determination (r) of 0.9998 and good back-calculated accuracy and precision. The intra- and inter-day precision (R.S.D.%) was lower than 10% and accuracy ranged from 85 to 115%. The lower limit of quantification was identifiable and reproducible at 0.5 ng/ml with 0.2 ml plasma. The proposed method enables the unambiguous identification and quantification of lafutidine for pharmacokinetic, bioavailability or bioequivalence studies.

Acetamides↗

PubMed2005

Determination of limonin in rat plasma by liquid chromatography-electrospray mass spectrometry.

A simple, sensitive and selective liquid chromatography coupled with electrospray ionization mass spectrometry (LC/ESI/MS) method for determination of limonin (LM) in rat plasma has been developed and validated. The method had advantages of a single liquid-liquid extraction with ether and high sensitivity. Analyses were conducted at a flow rate of 0.2 ml/min by a gradient elution. The detection utilized selected ion monitoring in the negative ion mode at m/z 460.00 and 423.15 for the deprotonated molecular ions of LM and the internal standard, respectively. The quantitation limit for LM in rat plasma was 1.0 ng/ml. The linearity was also excellent over the concentration range of 1.9-500 ng/ml of LM. The intra- and inter-day precision (relative standard deviation (R.S.D.%)) was lower than 10% and accuracy ranged from 90 to 110%, showing a good reproducibility. This developed method was successfully applied to analysis of LM in biological fluids.

Animals↗

PubMed2005

Adeno-associated virus mediated interferon-gamma inhibits the progression of hepatic fibrosis in vitro and in vivo.

AIM: To investigate the effects of adeno-associated virus (AAV) mediated expression of human interferon-gamma for gene therapy in experimental hepatic fibrosis in vitro and in vivo. METHODS: We constructed the recombinant AAV encoding human INF-gamma (rAAV- INF-gamma) and took the primary rat hepatic stellate cells and carbon tetrachloride induced rats as the experimental hepatic fibrosis model in vitro and in vivo. Immunocytochemistry analysis was used to reveal the expression of alpha-SMA, the marker protein expressed in hepatic stellate cells. The mRNA expression of TGF-beta, TIMP-1, and MMP-13 were analyzed by RT-PCR method. In vivo study, the hydroxyproline content in liver and serum AST, ALT were also detected. RESULTS: In vitro study, AAV vector could mediated efficient expression of human INF-gamma, which inhibit the activation of hepatic stellate cells, decrease the expression of alpha-SMA and mRNA of TIMP-1, TGF-beta, with the MMP-13 unchanged. In vivo study, the histological examination revealed that rAAV- INF-gamma could inhibit the progression of the hepatic fibrosis. In the rAAV-INF-gamma induced group, the hydroxyproline content and serum AST, ALT level were decreased to 177+/-28 microg/g wet liver, 668.5+/-140.0, 458.4+/-123.5 U/L, compare with the fibrosis control group 236+/-31 microg/g wet liver, 1 019.1+/-276.3, 770.5+/-154.3 U/L, respectively (P<0.01). mRNA expression of TIMP-1 in the rAAV-INF-gamma induced rat liver was decreased while no significant change was observed in TGF-beta and MMP-13. CONCLUSION: All these results indicated that rAAV-INF-gamma has potential effects for gene therapy of hepatic fibrosis, which could inhibit the progression of hepatic fibrosis.

Animals↗

PubMed2005

High performance liquid chromatographic-mass spectrometric determination of ginsenoside Rg3 and its metabolites in rat plasma using solid-phase extraction for pharmacokinetic studies.

To support pharmacokinetic studies of ginsenosides, a novel method to quantitatively analyze ginsenoside Rg3 (Rg3), its prosapogenin ginsenoside Rh2 (Rh2) and aglycone 20(S)-protopanaxadiol (ppd) in rat plasma was developed and validated. The method was based on gradient separation of ginsenosides present in rat plasma using high performance liquid chromatography (HPLC), followed by detection with electrospray ionization(ESI) mass spectrometry (MS) in negative ion mode with the mobile phase additive, ammonium chloride (500 microM). Differentiation of ginsenosides was achieved through simultaneous detection of the [M(+)Cl(-)] adduct of ginsenoside Rg3 and [M(+)Cl(-)] adducts of its deglycosylated metabolites Rh2 and ppd, and other ions after solid phase extraction (SPE). The /specific ions monitored were m/z 819.50 for Rg3, m/z 657.35 for Rh2, m/z 495.40 for ppd and m/z 799.55 for the internal standard (digitoxin). The mean recoveries for Rg3, Rh2 and ppd were 77.85, 82.65 and 98.33%, respectively using 0.1 ml plasma for extraction. The lower limits of quantification were 10.0, 2.0 and 8.0 ng/ml (equivalent to 0.1, 0.02 and 0.08 ng in each 10 microl injection onto the HPLC column) for Rg3, Rh2 and ppd, respectively. The method has been demonstrated to be highly sensitive and accurate for the determination of Rg3 and its metabolites in rat plasma.

Animals↗

PubMed2005

Uptake and metabolism of ginsenoside Rh2 and its aglycon protopanaxadiol by Caco-2 cells.

The uptake and metabolism profiles of ginsenoside Rh2 and its aglycon protopanaxadiol (ppd) were studied in the human epithelial Caco-2 cell line. High-performance liquid chromatography-mass spectrometry was applied to determine Rh2 and its aglycon ppd concentration in the cells at different pH, temperature, concentration levels and in the presence or absence of inhibitors. Rh2 uptake was time and concentration dependent, and its uptake rates were reduced by metabolic inhibitors and influenced by low temperature, thus indicating that the absorption process was energy-dependent. Drug uptake was maximal when the extracellular pH was 7.0 for Rh2 and 8.0 for ppd. Rh2 kinetic analysis showed that a non-saturable component (Kd 0.17 nmol x h(-1) x mg(-1) protein) and an active transport system with a Km of 3.95 micromol x l(-1) and a Vmax of 4.78 nmol x h(-1) x mg(-1)protein were responsible for the drug uptake. Kinetic analysis of ppd showed a non-saturable component (Kd 0.78 nmol x h(-1) x mg(-1) protein). It was suggested that active extrusion of P-glycoprotein and drug degradation in the intestine may influence Rh2 bioavailability.

Caco-2 Cells↗