Biomedical subjects

Dafang Zhong

Publications and source records attributed to Dafang Zhong.

53 records · Page 3Linked to original sources

PubMed2004

pH-dependent geometric isomerization of roxithromycin in simulated gastrointestinal fluids and in rats.

The biotransformation of roxithromycin in simulated gastrointestinal fluids at 37 degrees C and in rats was investigated by using liquid chromatography-tandem mass spectrometry. Roxithromycin degraded to its Z-isomer and decladinose derivative in simulated gastrointestinal fluids in vitro at pH </= 3, and followed pseudo first-order degradation with a rate constant (+/-SD, standard derivation) of 0.1066 min(-1) (+/-0.0014) at pH 1.0, 0.0994 min(-1) (+/-0.0031) at pH 1.2, 0.0400 min(-1) (+/-0.0003) at pH 1.3, 0.0136 min(-1) (+/-0.0008) at pH 1.8, and 0.0022 min(-1) (+/-0.0002) at pH 3.0, respectively. The ratio of Z-roxithromycin to roxithromycin (+/-SD) was 0.21 (+/-0.01) at pH 1.0, 0.19 (+/-0.03) at pH 1.2, 0.18 (+/-0.01) at pH 1.3, 0.15 (+/-0.01) at pH 1.8, and 0.08 (+/-0.02) at pH 3.0, respectively. Pepsin and NaCl added to gastric fluid had no effect on the transformation of roxithromycin. Roxithromycin underwent four metabolic routes such as geometric isomerization, demethylation, dealkylation, and hydrolysis of cladinose in rats after oral administration. The geometric isomerization in rats was neither observed after an intravenous dose, nor after an oral dose with Na(2)CO(3) alkalization. The geometric isomerization between roxithromycin and its Z-isomer took place in gastric fluid both in vitro and in vivo. It was interconvertible and pH-dependent. The isomerization of roxithromycin to its Z-isomer was less than that of Z- to E-configuration both in vitro and in vivo.

Animals↗

PubMed2004

Development of a dissolution medium for nimodipine tablets based on bioavailability evaluation.

A marked difference in the dissolution rate between two brands of nimodipine tablets was observed using a newly developed dissolution medium of pH 4.5 acetate buffer containing 0.05% sodium dodecyl sulfate (SDS). However, when pH 4.5 acetate buffer containing 0.3% SDS was used as dissolution medium, which was specified in the edition, the dissolution results of the both brands conformed to the BP requirements and no significant difference in dissolution was observed. The dissolution data obtained for two commercial brands of nimodipine tablets indicate the superiority of the proposed system as a discriminatory dissolution medium for nimodipine tablets. The relative bioavailability of the two brands of nimodipine tablets was determined in healthy adult volunteers after a single dose in a randomized crossover study. Plasma concentrations were determined by a liquid chromatography-tandem mass spectrometry method. Statistical comparison of the AUC(0-T), AUC(0- infinity), C(max), and T(max) indicated a significant difference in the two brands of nimodipine tablets.

Adult↗

PubMed2004

Identification of a novel variant CYP2C9 allele in Chinese.

OBJECTIVES: Cytochrome P450 (CYP) 2C9 metabolizes about 16% of drugs in current clinical use, including lornoxicam and tolbutamide. SNPs in the CYP2C9 gene have increasingly been recognized as determinants of the metabolic phenotype that underlies interindividual and ethnic differences. METHODS: The present study focused on a Chinese poor metabolizer (PM) whose apparent genotype (CYP2C9*1/CYP2C9*3) did not agree with his PM phenotype for both lornoxicam and tolbutamide. By sequencing his CYP2C9 gene, we identified a new variant CYP2C9 allele involving a T269C transversion in exon 2 that leads to a Leu90Pro substitution in the encoded protein. RESULTS: The CYP2C9 genotype analysis in the family of the poor metabolizer showed the new exon 2 change and CYP2C9*3 occurred on different alleles. Thus, the PM status of this subject could be attributed to his being heterozygous for the CYP2C9 T269C allele together with the CYP2C9*3. Frequency analysis in 147 unrelated Chinese males indicated approximately 2% of the Chinese population carry the allele. CONCLUSION: This study suggests that this novel CYP2C9 allele was correlated with reduced plasma clearance of drugs that are substrates for CYP2C9.

3' Untranslated Regions↗

PubMed2004

Anti-tussive activity of benproperine enantiomers on citric-acid-induced cough in conscious guinea-pigs.

The anti-tussive effect of the R-(+)- and S-(-)-enantiomers of benproperine was evaluated and compared with that of the racemate on cough induced by 7.5% citric acid in conscious guinea-pigs. All the three compounds, intraperitoneally administered 1.5 h before the test, significantly inhibited citric-acid-induced cough. The ID50 values (effective doses for 50% inhibition) (with 95% confidence intervals) were 16.1 (9.1-28.4), 23.3 (11.2-48.6), 25.4 (11.7-55.1) mg kg(-1) for the number of coughs in the 3 min of challenge, and 11.9 (5.3-26.6), 13.5 (5.6-32.4), 19.2 (12.8-28.9) mg kg(-1) for the number of coughs in the 5 min immediately after the challenge, for (+/-)-benproperine, R-(+)-benproperine and S-(-)-benproperine, respectively. These findings suggest that the use of either enantiomer does not show any advantage over the racemate with regard to their anti-tussive effect.

Animals↗

PubMed2003

Determination of vertilmicin in rat serum by high-performance liquid chromatography using 1-fluoro-2,4-dinitrobenzene derivatization.

A procedure for the high-performance liquid chromatographic determination of vertilmicin in rat serum was described using pre-column derivatization. The serum proteins were precipitated with acetonitrile and vertilmicin in the supernatant was derivatized with 1-fluoro-2,4-dinitrobenzene. Etimicin was selected as the internal standard. The mobile phase consisted of methanol--20mM ammonium acetate (80:20, v/v), and flow-rate was 0.9 ml/min. Ultraviolet detection was set at 365 nm. The reaction products were chromatographed on a C(18) column kept at 40 degrees C. A good linearity was found in the range of 0.5-250 microg/ml. Both intra- and inter-day precisions of vertilmicin, expressed as the relative standard deviation, were less than 7.4%. Accuracy, expressed as the relative error, ranged from -0.1 to 3.6%. The mean absolute recovery of vertilmicin at three different concentrations was 92.5%. Serum volumes of 50 microl were sufficient for the determination of vertilmicin. The method was proved suitable for the pharmacokinetic study of vertilmicin in rats.

Aminoglycosides↗

PubMed2003

Determination of scutellarin in rat plasma by high-performance liquid chromatography with ultraviolet detection.

A validated high-performance liquid chromatography method is described for the determination of scutellarin in rat plasma using a liquid-liquid extraction and ultraviolet (UV) absorbance detection. The separation used a Diamonsil ODS column (250 mm x 4.6mm i.d., 5 microm particle size) with an isocratic mobile phase consisting of methanol-acetonitrile-50mM dihydrogen ammonium phosphate buffer (22:15:63 (v/v/v), adjusted to pH 2.5 with 1M phosphoric acid). The ultraviolet detector operated at 335 nm. Plasma samples were extracted with ethyl acetate after acidification. The extraction recovery of scutellarin ranged from 68.1 to 80.5%. High selectivity and a low quantitation limit (0.050 microg/ml) were achieved. The linear range was 0.050-12.5 microg/ml, correlation coefficient r=0.9981. The method has a good reproducibility, R.S.D. values were below 7.9% for within-day and between-day precision. The method is simple, rapid, and applicable to preliminary pharmacokinetic studies of scutellarin in rats.

Animals↗

PubMed2003

Determination of three major components of bitespiramycin and their major active metabolites in rat plasma by liquid chromatography-ion trap mass spectrometry.

The rapid, selective and sensitive liquid chromatographic-ion trap mass spectrometric (LC-MS(n)) method was developed and validated for determination of three major components (isovaleryspiramycins, ISV-SPMs) of a novel macrolide antibiotic bitespiramycin and their major active metabolites (spiramycins, SPMs) in rat plasma. The analytes ISV-SPMs, SPMs, internal standard roxithromycin and azithromycin were extracted from plasma samples by liquid-liquid extraction, and chromatographed on a C(18) column using two mobile phase systems. Detection was carried out on an ion trap mass spectrometer by selected reaction monitoring (SRM) mode via electrospray ionization (ESI). Three components (ISV-SPM I, II, III or SPM I, II, III) could be simultaneously determined within 6.5 min. Linear calibration curves were obtained in the concentration ranges of 4-200 ng/ml for ISV-SPM I and SPM I, 12-600 ng/ml for ISV-SPM II and SPM II, and 18-900 ng/ml for ISV-SPM III and SPM III. The intra- and inter-run precision (RSD), calculated from quality control (QC) samples were less than 8.8 and 10.4% for ISV-SPMs, and 9.3 and 11.2% for SPMs, respectively. The method was applied for the evaluation of the pharmacokinetics of bitespiramycin in rats following peroral/intravenous administration.

Animals↗

PubMed2003

Determination of cefaclor in human plasma by a sensitive and specific liquid chromatographic-tandem mass spectrometric method.

A sensitive and specific liquid chromatographic-tandem mass spectrometric method is described for the determination of cefaclor in human plasma. The plasma samples were treated by two sample preparation procedures, i.e. protein precipitation (PPT) and solid-phase extraction (SPE). The pretreated samples were analyzed on a C(18) HPLC column interfaced with a triple quadrupole tandem mass spectrometer. Positive electrospray ionization (ESI) was employed as the ionization source. The analyte and internal standard ampicillin (for PPT) or cefetamet (for SPE) were detected by use of selected reaction monitoring (SRM) mode. The lower limit of quantitation obtained as a result of the PPT procedure was 100 ng/ml. The intra- and inter-run precision, calculated from quality control (QC) samples was less than 12% for cefaclor. The accuracy as determined from QC samples was within +/-3% for the analyte. The SPE procedure could provide the lower limit of quantitation of 2 ng/ml. The precision and accuracy were measured to be below 7.1% and between -3.6% and 1.1%, respectively, for all QC samples. The method was applied for the evaluation of the pharmacokinetic profiles of cefaclor sustained-release formulation.

Anti-Bacterial Agents↗

PubMed2003

Determination of ketotifen and its conjugated metabolite in human plasma by liquid chromatography/tandem mass spectrometry: application to a pharmacokinetic study.

A sensitive and specific liquid chromatography/tandem mass spectrometry (LC/MS/MS) method was developed for the investigation of the pharmacokinetics of ketotifen and its major metabolite, ketotifen N-glucuronide, in human plasma. The plasma samples were treated by liquid-liquid extraction and analyzed using LC/MS/MS with an electrospray ionization interface. Diphenhydramine was used as the internal standard. The method had a lower limit of quantitation of 10 pg/mL for ketotifen, which offered increased sensitivity, selectivity and speed of analysis, compared with existing methods. The intra- and inter-day precision were measured to be below 8.2% and accuracy between -2.4% and 3.4% for all QC samples. Incubation of the plasma samples with beta-glucuronidase allowed the quantitation of ketotifen N-glucuronide. This quantitation method was successfully applied to a pharmacokinetic study of ketotifen and its major metabolite after oral administration of 2 mg ketotifen fumarate to 16 healthy volunteers.

Adult↗

PubMed2003

Determination of carbocysteine in human plasma by liquid chromatography/tandem mass spectrometry employing precolumn derivatization.

A sensitive liquid chromatography/tandem mass spectrometry (LC/MS/MS) method was developed to determine carbocysteine in human plasma using 2-pyridylacetic acid as the internal standard (IS). The method employed derivatization with 10 M hydrochloric acid/methanol, which significantly improved the ionization efficiency of carbocysteine. After methanol-induced protein precipitation of plasma samples, carbocysteine and the IS were derivatized and subjected to LC/MS/MS analysis using atmospheric pressure chemical ionization. The method has a lower limit of quantitation of 20 ng/mL for a 0.2-mL plasma aliquot. The intra- and inter-day precision (RSD), calculated from quality control (QC) samples, was less than 7%. The accuracy, determined using QC samples, was within +/- 1%. The method offered increased sensitivity, selectivity and speed of analysis over existing methods. The method was utilized to support clinical pharmacokinetic studies of carbocysteine in volunteers following oral administration.

Calibration↗

PubMed2003

Identification of the metabolites of 9-nitro-20(S)-camptothecin in rats.

9-Nitro-20(S)-camptothecin is a novel anticancer drug. In this study, metabolites of 9-nitro-20(S)-camptothecin in rats were identified. Rats were dosed with the drug, and the metabolites in the bile were isolated and collected by high-performance liquid chromatography using a gradient elution. By LC/MSn(n =1-3), the biliary metabolites in addition to the unchanged drug were identified as 9-amino-20(S)-camptothecin (M3), 9-acetamido-20(S)-camptothecin (M4), and the glucuronide of 9-hydroxy-20(S)-camptothecin (M1) with the aid of the reference substances and the enzymatic hydrolysis. The accurate mass data for metabolites M2 and M5 were determined by a quadrupole time-of-flight mass spectrometer. Metabolite M5 was suggested to be the glutathione conjugate of 10-hydroxy-20(S)-campto-thecin, and M2 may arise from the loss of glutamic acid from M5. Metabolites M1 and M3 were also found in the urine, and M4 in the feces. Fecal metabolite M7 was confirmed to be 9-hydroxy-20(S)-camptothecin (the aglycon of M1) by being compared with the reference standard. The mercapturic acid conjugate of 10-hydroxy-20(S)-camptothecin (M6) was detected in the urine and feces by LC/MSn

Animals↗

PubMed2002

Enantioselective total synthesis of (-)-strychnine using the catalytic asymmetric Michael reaction and tandem cyclization.

The enantioselective total synthesis of (-)-strychnine was accomplished through the use of the highly practical catalytic asymmetric Michael reaction (0.1 mol % of (R)-ALB, more than kilogram scale, without chromatography, 91% yield and >99% ee) as well as a tandem cyclization that simultaneously constructed B- and D-rings (>77% yield). Moreover, newly developed reaction conditions for thionium ion cyclization, NaBH3CN reduction of the imine moiety in the presence of Lewis acid to prevent ring opening reaction, and chemoselective reduction of the thioether (desulfurization) in the presence of exocyclic olefin were pivotal to complete the synthesis. The described chemistry paves the way for the synthesis of more advanced Strychnos alkaloids.

Cyclization↗

PubMed2002

Quantitation of the flavonoid wogonin and its major metabolite wogonin-7 beta-D-glucuronide in rat plasma by liquid chromatography-tandem mass spectrometry.

This study described the application of liquid chromatography-tandem mass spectrometry for the quantitation of wogonin and its major metabolite in rat plasma. Only one conjugated metabolite with glucuronic acid was identified by chromatographic and electrospray multi-stage mass spectrometric assay. A derivatization reaction with 2-chlorethanol further demonstrated that the metabolite was wogonin-7 beta-D-glucuronide (W-7-G), not wogonin-5 beta-D-glucuronide. Other conjugated metabolites, e.g., sulfates and glucosides, were not detected. The plasma concentration of free wogonin was determined using atmospheric pressure chemical ionization source in the selected reaction monitoring mode. The method had a lower limit of quantitation of 0.25 ng/ml for wogonin, which offered increased sensitivity, selectivity and speed of analysis over an existing method. Incubation of the plasma samples with beta-glucuronidase allows the quantitation of W-7-G. This quantitation method was successfully applied to a preclinical pharmacokinetic study of wogonin and its major metabolite, W-7-G, after an oral administration of 5 mg/kg wogonin to rats.

Animals↗

PubMed2002

Isolation and identification of the glucuronide of 4-(3H-1,2-dihydro-1-pyrrolizinone-2-methylamino)benzoic acid from rabbit urine.

The metabolic profile of 3H-1,2-dihydro-2-(4-methylphenylamino)methyl-1-pyrrolizinone (SFZ-47), a putative non-steroidal anti-inflammatory pro-drug, has been studied in rabbit urine. Semi-preparative reversed-phase HPLC of 24 h urine from two rabbits given single oral doses of SFZ-47 (200 mg) allowed the separation of SFZ-47 together with the oxidative metabolite 4-(3H-1,2-dihydro-1-pyrrolizinone-2-methylamino)benzoic acid (SFZ-47-COOH) and its glucuronide conjugate. The glucuronide was characterized by ESI-MS(n) and (1)H NMR and shown to be the 1-O-acyl beta-D-glucuronide conjugate of SFZ-47-COOH. The method gave excellent resolution of the glucuronide from endogenous constituents in urine and may be suitable for the preparation of glucuronide metabolites of other drugs.

Animals↗

PubMed2002

Sensitive and specific liquid chromatographic-tandem mass spectrometric assay for dihydroergotamine and its major metabolite in human plasma.

A sensitive and specific procedure for the simultaneous determination of dihydroergotamine (DHE) and its 8'-hydroxylated metabolite (8'-OH-DHE) in human plasma was developed and validated. The analytes were extracted from plasma samples by liquid-liquid extraction, separated through a Zorbax C18 column (50x2.1 mm I.D.) and detected by tandem mass spectrometry with an electrospray ionization interface. Caroverine was used as the internal standard. The method has a lower limit of quantitation (LOQ) of 10.0 and 11.0 pg/ml for DHE and 8'-OH-DHE, respectively. The intra- and inter-run precision was measured to be below 9.1% for both DHE and 8'-OH-DHE. The inter-run accuracy was within 4% for the analytes. The overall extraction recoveries of DHE and 8'-OH-DHE were determined to be about 58 and 52% on average, respectively. The chromatographic run time was approximately 2.5 min. More than 120 samples could be assayed daily with this method, including sample preparation, data acquisition and processing. The method developed was successfully used to investigate plasma concentrations of DHE and 8'-OH-DHE in a pharmacokinetic study of volunteers who received DHE orally.

Chromatography, Liquid↗

PubMed2002

Study of the electrospray ionization tandem mass spectrometry of sildenafil derivatives.

A detailed analysis of the product ion spectrum generated from the protonated molecule of sildenafil (Viagra(R)) under multiple tandem mass spectrometry (ESI-MS(n)) conditions using an ion-trap mass spectrometer is reported. Molecular composition data of the fragment ions were obtained with the aid of comparisons of the multiple tandem mass spectra of eight sildenafil derivatives in two series, the structures of which are identical except for some substituted alkyl groups. Attempts have been made to provide rational pathways for the formation of the fragment ions from these protonated sildenafil derivatives. The structure-fragmentation relationships will facilitate the characterization of the structures of other sildenafil analogs.

Piperazines↗

PubMedDate not supplied

Simultaneous determination of pantoprazole and its two metabolites in dog plasma by HPLC.

A simple and sensitive high-performance liquid chromatography (HPLC) method is developed and validated for simultaneous determination of pantoprazole and its two metabolites (pantoprazole sulfone and pantoprazole thioether) in dog plasma and applied to a pharmacokinetic study in Beagle dogs. Following a protein precipitation procedure, the samples are separated using reversed-phase HPLC (C18) by a gradient of acetonitrile and ammonium acetate (pH 6.0) at a flow rate of 1.0 mL/min and quantitated using UV detection at 290 nm. Omeprazole is selected as the internal standard. The method has a lower limit of quantitation of 0.025 microg/mL for pantoprazole and its two metabolites, using 0.1-mL aliquots of plasma. The linear calibration curves are obtained in the concentration range of 0.025-10.0 microg/mL for three analytes. The intra- and interrun precision (relative standard deviation), calculated from quality control (QC) samples, is less than 13% for three analytes. The accuracy determined from QC samples is between -6.4% and 12%.

2-Pyridinylmethylsulfinylbenzimidazoles↗